可溶性HLA-G二聚体抑制同种T细胞应答的研究
|
摘要
MHC型别不同的供/受者间进行移植后会发生强烈的排斥反应,其机制主要是同种反应性T细胞(简称同种T细胞)识别同种异体组织抗原(简称同种抗原)并产生应答。大量免疫抑制剂的应用过度的抑制了机体的免疫系统,使受者处于罹患严重感染的风险之中,因而诱导同种异体耐受成为亟待解决的问题。HLA-G是一种非经典的HLAⅠ类分子,其限制性的组织分布、有限的基因多态性提示其为一种诱导免疫耐受的分子。体外研究资料显示HLA-G通过与抑制性受体的结合诱导T、B、NK、DC、巨噬细胞等免疫细胞的免疫耐受,临床病例研究也显示HLA-G阳性的受者与阴性受者相比,急性排斥期缩短,慢性排斥发生率降低。最新研究表明HLA-G二聚体形式对于HLA-G与抑制性受体的结合以及生物学功能的发挥都起着至关重要的作用。本研究采用基因工程技术构建并制备了可溶性HLA-G二聚体,并利用混合淋巴细胞培养模型研究了该分子抑制同种T细胞应答的作用。论文分为2个部分,主要内容与结果如下:
一﹑可溶性HLA-G二聚体的制备
本研究利用基因工程技术将编码HLA-G重链胞外段(α1-α3区)的基因与编码人IgG-Fc段的基因融合插入到真核表达载体pcDNA3.1+中形成pcDNA3.1+[sHLA-G/IgG]质粒。通过电穿孔技术将质粒导入HLAⅠ类分子和IgG重链缺陷的721.221细胞中表达,筛选出高效表达的稳定转染子(dimer-721.221),经特异性ELISA和western blotting鉴定表达的HLA-G/IgG融合蛋白具有正确的分子量和空间构象,并通过IgG-Fc段形成了二聚体,将该融合蛋白命名为可溶性HLA-G二聚体。
二﹑可溶性HLA-G二聚体抑制同种T细胞应答的研究
本研究利用灭活的T1与HLA阴性的健康人外周血淋巴细胞的混合淋巴细胞培养模型模拟同种反应,研究了HLA-G二聚体抑制同种T细胞应答的作用。结果显示,HLA-G二聚体在纳摩尔水平抑制同种T细胞应答:抑制同种反应性CD8+、CD4+T细胞的活化和增殖,抑制同种CTL细胞的产生,并且这种抑制作用比HLA-G单体要强。此外,HLA-G二聚体还可上调同种反应性CD8+T细胞表面ILT2的表达,而这种作用又可进一步促进HLA-G二聚体的抑制功能。鉴于HLA-G二聚体与受体的高亲和力以及抑制同种T细胞应答的高效率,该分子可望应用于HLA-G/受体的结合研究以及诱导同种移植耐受。
本研究的创新点和意义:
1.本研究首次利用基因工程技术构建、表达了可溶性HLA-G二聚体,证实了该分子在纳摩尔水平抑制同种反应性T细胞的活化和增殖、抑制同种CTL的产生;
2.本研究首次将HLA-G二聚体与HLA-G单体在抑制同种反应性T细胞增殖方面的功能进行了比较,并证实HLA-G二聚体比单体更高效;
3.本研究首次报导了HLA-G在蛋白水平上调同种反应性CD8+T细胞表面ILT2的表达,这种上调作用又可进一步促进HLA-G二聚体的功能;
本研究制备的HLA-G二聚体将有利于HLA-G/受体的结合研究,并应用于诱导同种移植耐受。
HLA-G, a non-classical HLA class I molecule, induces a wide range of tolerogenic immunological effects via interaction with its inhibitory receptors. However, recent studies show that HLA-G dimer formation is essential to bind to its receptors and exhibit its effects. In this study, a soluble divalent HLA-G/IgG molecule (sHLA-G dimer) was constructed. Its inhibitory effect on T-cell alloresponse was studied with mixed lymphocyte reaction (MLR) in vitro, which was set up by mixing inactivated T1 cells with HLA-mismatched peripheral blood lymphocytes (PBLs) in the presence or absence of the sHLA-G dimer. The results show that sHLA-G dimer inhibits T-cell alloresponse by reducing proliferation of both CD4+ and CD8+ T cells and suppressing generation of allo-reactive CTLs at nanomole concentration. The inhibition of the sHLA-G dimer is observed to be more effective than that of sHLA-G monomer. Our results also indicate sHLA-G dimer up-regulates inhibitory receptor ILT2 on allo-reactive CD8+ T cells, which contributes to the significant inhibition on T-cell alloresponse. The sHLA-G dimer molecule may have implications for allo-transplantation.
一﹑可溶性HLA-G二聚体的制备
本研究利用基因工程技术将编码HLA-G重链胞外段(α1-α3区)的基因与编码人IgG-Fc段的基因融合插入到真核表达载体pcDNA3.1+中形成pcDNA3.1+[sHLA-G/IgG]质粒。通过电穿孔技术将质粒导入HLAⅠ类分子和IgG重链缺陷的721.221细胞中表达,筛选出高效表达的稳定转染子(dimer-721.221),经特异性ELISA和western blotting鉴定表达的HLA-G/IgG融合蛋白具有正确的分子量和空间构象,并通过IgG-Fc段形成了二聚体,将该融合蛋白命名为可溶性HLA-G二聚体。
二﹑可溶性HLA-G二聚体抑制同种T细胞应答的研究
本研究利用灭活的T1与HLA阴性的健康人外周血淋巴细胞的混合淋巴细胞培养模型模拟同种反应,研究了HLA-G二聚体抑制同种T细胞应答的作用。结果显示,HLA-G二聚体在纳摩尔水平抑制同种T细胞应答:抑制同种反应性CD8+、CD4+T细胞的活化和增殖,抑制同种CTL细胞的产生,并且这种抑制作用比HLA-G单体要强。此外,HLA-G二聚体还可上调同种反应性CD8+T细胞表面ILT2的表达,而这种作用又可进一步促进HLA-G二聚体的抑制功能。鉴于HLA-G二聚体与受体的高亲和力以及抑制同种T细胞应答的高效率,该分子可望应用于HLA-G/受体的结合研究以及诱导同种移植耐受。
本研究的创新点和意义:
1.本研究首次利用基因工程技术构建、表达了可溶性HLA-G二聚体,证实了该分子在纳摩尔水平抑制同种反应性T细胞的活化和增殖、抑制同种CTL的产生;
2.本研究首次将HLA-G二聚体与HLA-G单体在抑制同种反应性T细胞增殖方面的功能进行了比较,并证实HLA-G二聚体比单体更高效;
3.本研究首次报导了HLA-G在蛋白水平上调同种反应性CD8+T细胞表面ILT2的表达,这种上调作用又可进一步促进HLA-G二聚体的功能;
本研究制备的HLA-G二聚体将有利于HLA-G/受体的结合研究,并应用于诱导同种移植耐受。
HLA-G, a non-classical HLA class I molecule, induces a wide range of tolerogenic immunological effects via interaction with its inhibitory receptors. However, recent studies show that HLA-G dimer formation is essential to bind to its receptors and exhibit its effects. In this study, a soluble divalent HLA-G/IgG molecule (sHLA-G dimer) was constructed. Its inhibitory effect on T-cell alloresponse was studied with mixed lymphocyte reaction (MLR) in vitro, which was set up by mixing inactivated T1 cells with HLA-mismatched peripheral blood lymphocytes (PBLs) in the presence or absence of the sHLA-G dimer. The results show that sHLA-G dimer inhibits T-cell alloresponse by reducing proliferation of both CD4+ and CD8+ T cells and suppressing generation of allo-reactive CTLs at nanomole concentration. The inhibition of the sHLA-G dimer is observed to be more effective than that of sHLA-G monomer. Our results also indicate sHLA-G dimer up-regulates inhibitory receptor ILT2 on allo-reactive CD8+ T cells, which contributes to the significant inhibition on T-cell alloresponse. The sHLA-G dimer molecule may have implications for allo-transplantation.
引文
1. Fujii, T., A. Ishitani, and D.E. Geraghty, A soluble form of the HLA-G antigen is encoded by a messenger ribonucleic acid containing intron 4. J Immunol, 1994. 153(12): p. 5516-24.
2. Ishitani, A. and D.E. Geraghty, Alternative splicing of HLA-G transcripts yields proteins with primary structures resembling both class I and class II antigens. Proc Natl Acad Sci U S A, 1992. 89(9): p. 3947-51.
3. Kirszenbaum, M., et al., An alternatively spliced form of HLA-G mRNA in human trophoblasts and evidence for the presence of HLA-G transcript in adult lymphocytes. Proc Natl Acad Sci U S A, 1994. 91(10): p. 4209-13.
4. Kovats, S., et al., A class I antigen, HLA-G, expressed in human trophoblasts. Science, 1990. 248(4952): p. 220-3.
5. Moreau, P., et al., Soluble HLA-G molecule. An alternatively spliced HLA-G mRNA form candidate to encode it in peripheral blood mononuclear cells and human trophoblasts. Hum Immunol, 1995. 43(3): p. 231-6.
6. Paul, P., et al., Identification of HLA-G7 as a new splice variant of the HLA-G mRNA and expression of soluble HLA-G5, -G6, and -G7 transcripts in human transfected cells. Hum Immunol, 2000. 61(11): p. 1138-49.
7. Creput, C., et al., Human leukocyte antigen-G (HLA-G) expression in biliary epithelial cells is associated with allograft acceptance in liver-kidney transplantation. J Hepatol, 2003. 39(4): p. 587-94.
8. Creput, C., et al., Detection of HLA-G in serum and graft biopsy associated with fewer acute rejections following combined liver-kidney transplantation: possible implications for monitoring patients. Hum Immunol, 2003. 64(11): p. 1033-8.
9. Le Rond, S., et al., Evidence to support the role of HLA-G5 in allograft acceptance through induction of immunosuppressive/ regulatory T cells. J Immunol, 2006. 176(5): p. 3266-76.
10. Le Rond, S., et al., Alloreactive CD4+ and CD8+ T cells express the immunotolerant HLA-G molecule in mixed lymphocyte reactions: in vivo implications in transplanted patients. Eur J Immunol, 2004. 34(3): p. 649-60.
11. Lila, N., et al., Human leukocyte antigen-G expression after heart transplantation is associated with areduced incidence of rejection. Circulation, 2002. 105(16): p. 1949-54.
12. Lila, N., et al., Implication of HLA-G molecule in heart-graft acceptance. Lancet, 2000. 355(9221): p. 2138.
13. Luque, J., et al., Soluble HLA-G in heart transplantation: their relationship to rejection episodes and immunosuppressive therapy. Hum Immunol, 2006. 67(4-5): p. 257-63.
14. Qiu, J., et al., Soluble HLA-G expression and renal graft acceptance. Am J Transplant, 2006. 6(9): p. 2152-6.
15. Colonna, M., et al., A common inhibitory receptor for major histocompatibility complex class I molecules on human lymphoid and myelomonocytic cells. J Exp Med, 1997. 186(11): p. 1809-18.
16. Colonna, M., et al., Human myelomonocytic cells express an inhibitory receptor for classical and nonclassical MHC class I molecules. J Immunol, 1998. 160(7): p. 3096-100.
17. Cosman, D., et al., A novel immunoglobulin superfamily receptor for cellular and viral MHC class I molecules. Immunity, 1997. 7(2): p. 273-82.
18. Ponte, M., et al., Inhibitory receptors sensing HLA-G1 molecules in pregnancy: decidua-associated natural killer cells express LIR-1 and CD94/NKG2A and acquire p49, an HLA-G1-specific receptor. Proc Natl Acad Sci U S A, 1999. 96(10): p. 5674-9.
19. Rajagopalan, S. and E.O. Long, A human histocompatibility leukocyte antigen (HLA)-G-specific receptor expressed on all natural killer cells. J Exp Med, 1999. 189(7): p. 1093-100.
20. Shiroishi, M., et al., Human inhibitory receptors Ig-like transcript 2 (ILT2) and ILT4 compete with CD8 for MHC class I binding and bind preferentially to HLA-G. Proc Natl Acad Sci U S A, 2003. 100(15): p. 8856-61.
21. Apps, R., et al., A homodimeric complex of HLA-G on normal trophoblast cells modulates antigen-presenting cells via LILRB1. Eur J Immunol, 2007. 37(7): p. 1924-37.
22. Boyson, J.E., et al., Disulfide bond-mediated dimerization of HLA-G on the cell surface. Proc Natl Acad Sci U S A, 2002. 99(25): p. 16180-5.
23. Gonen-Gross, T., et al., Complexes of HLA-G protein on the cell surface are important for leukocyte Ig-like receptor-1 function. J Immunol, 2003. 171(3): p. 1343-51.
24. Gonen-Gross, T., et al., Special organization of the HLA-G protein on the cell surface. Hum Immunol,2003. 64(11): p. 1011-6.
25. Shiroishi, M., D. Kohda, and K. Maenaka, Preparation and crystallization of the disulfide-linked HLA-G dimer. Biochim Biophys Acta, 2006. 1764(5): p. 985-8.
26. Shiroishi, M., et al., Efficient leukocyte Ig-like receptor signaling and crystal structure of disulfide-linked HLA-G dimer. J Biol Chem, 2006. 281(15): p. 10439-47.
27. Hu, H.M., et al., Immunological monitoring of patients with melanoma after peptide vaccination using soluble peptide/HLA-A2 dimer complexes. J Immunother (1997), 2004. 27(1): p. 48-59.
28. Wang, Y.D. and W.F. Chen, Detecting specific cytotoxic T lymphocytes against SARS-coronavirus with DimerX HLA-A2:Ig fusion protein. Clin Immunol, 2004. 113(2): p. 151-4.
29. Weng, X., et al., Peptide-dependent inhibition of alloreactive T-cell response by soluble divalent HLA-A2/IgG molecule in vitro. Transplantation, 2007. 84(10): p. 1298-306.
30. Burlingham, W.J., S.S. Ceman, and R. DeMars, Secretion and cell surface expression of IgG1 are impaired in human B lymphoblasts that lack HLA-A, -B, and -C antigens. Proc Natl Acad Sci U S A, 1989. 86(20): p. 8005-9.
31. Solheim, J.C., et al., Prominence of beta 2-microglobulin, class I heavy chain conformation, and tapasin in the interactions of class I heavy chain with calreticulin and the transporter associated with antigen processing. J Immunol, 1997. 158(5): p. 2236-41.
32.房崇芸,吴雄文,龚非力.可溶性人类白细胞抗原-G1 cDNA的克隆及序列分析.免疫学杂志, 2001. 17: p. 81-84.
33.陈浩,翁秀芳,吴雄文等.人β2m基因的克隆及表达.华中科技大学学报(医学版), 2004. 33(1): p. 1-4.
34.杨敬宁,吴雄文,梁智辉等.可溶性HLA-G1重链分子的构建、表达及纯化.中国免疫学杂志, 2005. 21(4): p. 287-290.
35. Ladasky, J.J., et al., Residue 3 of beta2-microglobulin affects binding of class I MHC molecules by the W6/32 antibody. Immunogenetics, 1999. 49(4): p. 312-20.
36. Tran, T.M., et al., The epitope recognized by pan-HLA class I-reactive monoclonal antibody W6/32 and its relationship to unusual stability of the HLA-B27/beta2-microglobulin complex. Immunogenetics, 2001. 53(6): p. 440-6.
37. Allan, D.S., et al., Tetrameric complexes of HLA-E, HLA-F, and HLA-G. J Immunol Methods, 2002. 268(1): p. 43-50.
38.吴雄文,梁智辉.实用免疫学实验技术.湖北科学技术出版社, 2001.
39. Demaria, S., et al., Soluble beta 2-microglobulin-free class I heavy chains are released from the surface of activated and leukemia cells by a metalloprotease. J Biol Chem, 1994. 269(9): p. 6689-94.
40. Dong, Y., et al., Soluble nonclassical HLA generated by the metalloproteinase pathway. Hum Immunol, 2003. 64(8): p. 802-10.
41. Park, G.M., et al., Soluble HLA-G generated by proteolytic shedding inhibits NK-mediated cell lysis. Biochem Biophys Res Commun, 2004. 313(3): p. 606-11.
42. Blaschitz, A., et al., The soluble pool of HLA-G produced by human trophoblasts does not include detectable levels of the intron 4-containing HLA-G5 and HLA-G6 isoforms. Mol Hum Reprod, 2005. 11(10): p. 699-710.
43. Salter RD, Howell DN, Cresswell P. Genes regulating HLA class I antigen expression in T-B lymphoblast hybrids. Immunogenetics 1985;21(3):235-246.
44. Bunce M, O'Neill CM, Barnardo MC, Krausa P, Browning MJ, Morris PJ et al. Phototyping: comprehensive DNA typing for HLA-A, B, C, DRB1, DRB3, DRB4, DRB5 & DQB1 by PCR with 144 primer mixes utilizing sequence-specific primers (PCR-SSP). Tissue Antigens 1995;46(5):355-367.
45. Hoefel D ,Grooby WL ,Monis PT,et al. A comparative study of carboxyfluorescein diacetate and carboxyfluorescein diacetate succinimidyl ester as indicators of bacterial activity. J Microbiol Methods, 2003, 52 :379-88.
46. AnguloR, Fulcher DA.Measurement of Candida-specifc blastogenesis :comparison of carboxyfluorescein succinimidyl ester labelling of T cells, thymidine incorporation , and CD69 expression. Cytometry, 1998, 34 :143-51.
47. Fulcher, D., Wong, S.,.Carboxyfluorescein succinimidyl ester-based proliferative assays for assessment of T-cell function in the diagnostic laboratory. Immunol. Cell Biol. 1999, 77:559.
48. Popma, S.H., Krasinskas, A.M., McLean, A.D., et al. Immune monitoring in xenotransplantation: the multiparameter flow cytometric mixed lymphocyte culture assay. Cytometry 2000. 42:277.
49. Babusikova, O., et al., Flow cytometric analysis of some activation/proliferation markers on humanthymocytes and their correlation with cell proliferation. Neoplasma, 1999. 46(6): p. 349-55.
50.Singal, D.P., Quantitative studies of alloantigen-reactive human lymphocytes in primary and secondary MLC. Hum Immunol, 1980. 1(1): p. 67-76.
51. Korzeniewski, C. and D.M. Callewaert, An enzyme-release assay for natural cytotoxicity. J Immunol Methods, 1983. 64(3): p. 313-20.
52. Reutelingsperger, C.P. and W.L. van Heerde, Annexin V, the regulator of phosphatidylserine-catalyzed inflammation and coagulation during apoptosis. Cell Mol Life Sci, 1997. 53(6): p. 527-32.
53. Rebmann, V., et al., Detection of HLA-G5 secreting cells. Hum Immunol, 2003. 64(11): p. 1017-24.
54. Kapasi, K., et al., HLA-G has a concentration-dependent effect on the generation of an allo-CTL response. Immunology, 2000. 101(2): p. 191-200.
55. Marchal-Bras-Goncalves, R., et al., A soluble HLA-G protein that inhibits natural killer cell-mediated cytotoxicity. Transplant Proc, 2001. 33(3): p. 2355-9.
56. Bainbridge, D.R., S.A. Ellis, and I.L. Sargent, HLA-G suppresses proliferation of CD4(+) T-lymphocytes. J Reprod Immunol, 2000. 48(1): p. 17-26.
57. Bahri, R., et al., Soluble HLA-G inhibits cell cycle progression in human alloreactive T lymphocytes. J Immunol, 2006. 176(3): p. 1331-9.
58. Feger, U., et al., HLA-G expression defines a novel regulatory T-cell subset present in human peripheral blood and sites of inflammation. Blood, 2007. 110(2): p. 568-77.
59. Contini, P., et al., Soluble HLA-A,-B,-C and -G molecules induce apoptosis in T and NK CD8+ cells and inhibit cytotoxic T cell activity through CD8 ligation. Eur J Immunol, 2003. 33(1): p. 125-34.
60. Fournel, S., et al., Cutting edge: soluble HLA-G1 triggers CD95/CD95 ligand-mediated apoptosis in activated CD8+ cells by interacting with CD8. J Immunol, 2000. 164(12): p. 6100-4.
61. Kanai, T., et al., A subclass of soluble HLA-G1 modulates the release of cytokines from mononuclear cells present in the decidua additively to membrane-bound HLA-G1. J Reprod Immunol, 2003. 60(2): p. 85-96.
62. Kanai, T., et al., Soluble HLA-G influences the release of cytokines from allogeneic peripheral blood mononuclear cells in culture. Mol Hum Reprod, 2001. 7(2): p. 195-200.
63. Poulton, T.A., et al., Changes in activation markers and cell membrane receptors on human peripheralblood T lymphocytes during cell cycle progression after PHA stimulation. Immunology, 1988. 64(3): p. 419-25.
64. Johannisson, A., et al., Effects of four trichothecene mycotoxins on activation marker expression and cell proliferation of human lymphocytes in culture. Cell Biol Toxicol, 1999. 15(4): p. 203-15.
65. Borges, L., et al., A family of human lymphoid and myeloid Ig-like receptors, some of which bind to MHC class I molecules. J Immunol, 1997. 159(11): p. 5192-6.
66. Cosman, D., N. Fanger, and L. Borges, Human cytomegalovirus, MHC class I and inhibitory signalling receptors: more questions than answers. Immunol Rev, 1999. 168: p. 177-85.
67. LeMaoult, J., et al., HLA-G up-regulates ILT2, ILT3, ILT4, and KIR2DL4 in antigen presenting cells, NK cells, and T cells. Faseb J, 2005. 19(6): p. 662-4.
1. Doherty, P.C. and R.M. Zinkernagel, A biological role for the major histocompatibility antigens. Lancet, 1975. 1(7922): p. 1406-9.
2. Svejgaard, A., P. Platz, and L.P. Ryder, HLA and disease 1982--a survey. Immunol Rev, 1983. 70: p. 193-218.
3. Ellis, S.A., M.S. Palmer, and A.J. McMichael, Human trophoblast and the choriocarcinoma cell lineBeWo express a truncated HLA Class I molecule. J Immunol, 1990. 144(2): p. 731-5.
4. Geraghty, D.E., B.H. Koller, and H.T. Orr, A human major histocompatibility complex class I gene that encodes a protein with a shortened cytoplasmic segment. Proc Natl Acad Sci U S A, 1987. 84(24): p. 9145-9.
5. Redman, C.W., et al., Class 1 major histocompatibility complex antigens on human extra-villous trophoblast. Immunology, 1984. 52(3): p. 457-68.
6. Schmidt, C.M. and H.T. Orr, A physical linkage map of HLA-A, -G, -7.5p, and -F. Hum Immunol, 1991. 31(3): p. 180-5.
7. Carosella, E.D., J. Dausset, and N. Rouas-Freiss, Immunotolerant functions of HLA-G. Cell Mol Life Sci, 1999. 55(3): p. 327-33.
8. Ishitani, A., et al., Protein expression and peptide binding suggest unique and interacting functional roles for HLA-E, F, and G in maternal-placental immune recognition. J Immunol, 2003. 171(3): p. 1376-84.
9. LeMaoult, J., et al., HLA-G1-expressing antigen-presenting cells induce immunosuppressive CD4+ T cells. Proc Natl Acad Sci U S A, 2004. 101(18): p. 7064-9.
10. Le Gal, F.A., et al., HLA-G-mediated inhibition of antigen-specific cytotoxic T lymphocytes. Int Immunol, 1999. 11(8): p. 1351-6.
11. Contini, P., et al., Soluble HLA-A,-B,-C and -G molecules induce apoptosis in T and NK CD8+ cells and inhibit cytotoxic T cell activity through CD8 ligation. Eur J Immunol, 2003. 33(1): p. 125-34.
12. Fournel, S., et al., Cutting edge: soluble HLA-G1 triggers CD95/CD95 ligand-mediated apoptosis in activated CD8+ cells by interacting with CD8. J Immunol, 2000. 164(12): p. 6100-4.
13. Messer, G., et al., HLA-J, a second inactivated class I HLA gene related to HLA-G and HLA-A. Implications for the evolution of the HLA-A-related genes. J Immunol, 1992. 148(12): p. 4043-53.
14. Heinrichs, H. and H.T. Orr, HLA non-A,B,C class I genes: their structure and expression. Immunol Res, 1990. 9(4): p. 265-74.
15. Davis, D.M., et al., Impaired spontaneous endocytosis of HLA-G. Eur J Immunol, 1997. 27(10): p. 2714-9.
16. Lee, N., et al., HLA-E is a major ligand for the natural killer inhibitory receptor CD94/NKG2A.Proc Natl Acad Sci U S A, 1998. 95(9): p. 5199-204.
17. Llano, M., et al., HLA-E-bound peptides influence recognition by inhibitory and triggering CD94/NKG2 receptors: preferential response to an HLA-G-derived nonamer. Eur J Immunol, 1998. 28(9): p. 2854-63.
18. He, X., et al., Identification of a novel HLA-F allele - HLA-F*010102. Tissue Antigens, 2004. 63(2): p. 181-3.
19. Ellis, S.A., et al., Evidence for a novel HLA antigen found on human extravillous trophoblast and a choriocarcinoma cell line. Immunology, 1986. 59(4): p. 595-601.
20. Ishitani, A. and D.E. Geraghty, Alternative splicing of HLA-G transcripts yields proteins with primary structures resembling both class I and class II antigens. Proc Natl Acad Sci U S A, 1992. 89(9): p. 3947-51.
21. Kirszenbaum, M., et al., An alternatively spliced form of HLA-G mRNA in human trophoblasts and evidence for the presence of HLA-G transcript in adult lymphocytes. Proc Natl Acad Sci U S A, 1994. 91(10): p. 4209-13.
22. Fujii, T., A. Ishitani, and D.E. Geraghty, A soluble form of the HLA-G antigen is encoded by a messenger ribonucleic acid containing intron 4. J Immunol, 1994. 153(12): p. 5516-24.
23. Blaschitz, A., et al., Endothelial cells in chorionic fetal vessels of first trimester placenta express HLA-G. Eur J Immunol, 1997. 27(12): p. 3380-8.
24. Crisa, L., et al., Identification of a thymic epithelial cell subset sharing expression of the class Ib HLA-G molecule with fetal trophoblasts. J Exp Med, 1997. 186(2): p. 289-98.
25. Hunt, J.S., et al., HLA-G and immune tolerance in pregnancy. Faseb J, 2005. 19(7): p. 681-93.
26. McMaster, M., et al., HLA-G isoforms produced by placental cytotrophoblasts and found in amniotic fluid are due to unusual glycosylation. J Immunol, 1998. 160(12): p. 5922-8.
27. Yang, Y., et al., Expression of HLA-G in human mononuclear phagocytes and selective induction by IFN-gamma. J Immunol, 1996. 156(11): p. 4224-31.
28. Parham, P., et al., Nature of polymorphism in HLA-A, -B, and -C molecules. Proc Natl Acad Sci U S A, 1988. 85(11): p. 4005-9.
29. Shimizu, Y., et al., Transfer and expression of three cloned human non-HLA-A,B,C class I majorhistocompatibility complex genes in mutant lymphoblastoid cells. Proc Natl Acad Sci U S A, 1988. 85(1): p. 227-31.
30. Dobbe, L.M., et al., Biochemical complexity of serum HLA class I molecules. Immunogenetics, 1988. 27(3): p. 203-10.
31. Paul, P., et al., Identification of HLA-G7 as a new splice variant of the HLA-G mRNA and expression of soluble HLA-G5, -G6, and -G7 transcripts in human transfected cells. Hum Immunol, 2000. 61(11): p. 1138-49.
32. Clements, C.S., et al., Crystal structure of HLA-G: a nonclassical MHC class I molecule expressed at the fetal-maternal interface. Proc Natl Acad Sci U S A, 2005. 102(9): p. 3360-5.
33. Lee, N., et al., The membrane-bound and soluble forms of HLA-G bind identical sets of endogenous peptides but differ with respect to TAP association. Immunity, 1995. 3(5): p. 591-600.
34. Diehl, M., et al., Nonclassical HLA-G molecules are classical peptide presenters. Curr Biol, 1996. 6(3): p. 305-14.
35. Munz, C., S. Stevanovic, and H.G. Rammensee, Peptide presentation and NK inhibition by HLA-G. J Reprod Immunol, 1999. 43(2): p. 139-55.
36. Boyson, J.E., et al., Disulfide bond-mediated dimerization of HLA-G on the cell surface. Proc Natl Acad Sci U S A, 2002. 99(25): p. 16180-5.
37. He, X., et al., Promiscuous antigen presentation by the nonclassical MHC Ib Qa-2 is enabled by a shallow, hydrophobic groove and self-stabilized peptide conformation. Structure, 2001. 9(12): p. 1213-24.
38. Khan, A.R., et al., The structure and stability of an HLA-A*0201/octameric tax peptide complex with an empty conserved peptide-N-terminal binding site. J Immunol, 2000. 164(12): p. 6398-405.
39. Strong, R.K., et al., HLA-E allelic variants. Correlating differential expression, peptide affinities, crystal structures, and thermal stabilities. J Biol Chem, 2003. 278(7): p. 5082-90.
40. Clements, C.S., et al., The production, purification and crystallization of a soluble form of the nonclassical MHC HLA-G: the essential role of cobalt. Acta Crystallogr Sect F Struct Biol Cryst Commun, 2006. 62(Pt 1): p. 70-3.
41. Shiroishi, M., D. Kohda, and K. Maenaka, Preparation and crystallization of the disulfide-linkedHLA-G dimer. Biochim Biophys Acta, 2006. 1764(5): p. 985-8.
42. Gonen-Gross, T., et al., Complexes of HLA-G protein on the cell surface are important for leukocyte Ig-like receptor-1 function. J Immunol, 2003. 171(3): p. 1343-51.
43. Gonen-Gross, T., et al., Special organization of the HLA-G protein on the cell surface. Hum Immunol, 2003. 64(11): p. 1011-6.
44. Morales, P.J., et al., Placental cell expression of HLA-G2 isoforms is limited to the invasive trophoblast phenotype. J Immunol, 2003. 171(11): p. 6215-24.
45. Shiroishi, M., et al., Efficient leukocyte Ig-like receptor signaling and crystal structure of disulfide-linked HLA-G dimer. J Biol Chem, 2006. 281(15): p. 10439-47.
46. Brown, D., J. Trowsdale, and R. Allen, The LILR family: modulators of innate and adaptive immune pathways in health and disease. Tissue Antigens, 2004. 64(3): p. 215-25.
47. Chapman, T.L., A.P. Heikeman, and P.J. Bjorkman, The inhibitory receptor LIR-1 uses a common binding interaction to recognize class I MHC molecules and the viral homolog UL18. Immunity, 1999. 11(5): p. 603-13.
48. Willcox, B.E., L.M. Thomas, and P.J. Bjorkman, Crystal structure of HLA-A2 bound to LIR-1, a host and viral major histocompatibility complex receptor. Nat Immunol, 2003. 4(9): p. 913-9.
49. Shiroishi, M., et al., Human inhibitory receptors Ig-like transcript 2 (ILT2) and ILT4 compete with CD8 for MHC class I binding and bind preferentially to HLA-G. Proc Natl Acad Sci U S A, 2003. 100(15): p. 8856-61.
50. Ponte, M., et al., Inhibitory receptors sensing HLA-G1 molecules in pregnancy: decidua-associated natural killer cells express LIR-1 and CD94/NKG2A and acquire p49, an HLA-G1-specific receptor. Proc Natl Acad Sci U S A, 1999. 96(10): p. 5674-9.
51. Rajagopalan, S. and E.O. Long, A human histocompatibility leukocyte antigen (HLA)-G-specific receptor expressed on all natural killer cells. J Exp Med, 1999. 189(7): p. 1093-100.
52. Rajagopalan, S., et al., Activation of NK cells by an endocytosed receptor for soluble HLA-G. PLoS Biol, 2006. 4(1): p. e9.
53. Yan, W.H. and L.A. Fan, Residues Met76 and Gln79 in HLA-G alpha1 domain involve in KIR2DL4 recognition. Cell Res, 2005. 15(3): p. 176-82.
54. Boyington, J.C., et al., Crystal structure of an NK cell immunoglobulin-like receptor in complex with its class I MHC ligand. Nature, 2000. 405(6786): p. 537-43.
55. Fan, Q.R., E.O. Long, and D.C. Wiley, Crystal structure of the human natural killer cell inhibitory receptor KIR2DL1-HLA-Cw4 complex. Nat Immunol, 2001. 2(5): p. 452-60.
56. Benichou, G., A. Valujskikh, and P.S. Heeger, Contributions of direct and indirect T cell alloreactivity during allograft rejection in mice. J Immunol, 1999. 162(1): p. 352-8.
57. Sayegh, M.H. and C.B. Carpenter, Role of indirect allorecognition in allograft rejection. Int Rev Immunol, 1996. 13(3): p. 221-9.
58. Schwartz, R.H., Costimulation of T lymphocytes: the role of CD28, CTLA-4, and B7/BB1 in interleukin-2 production and immunotherapy. Cell, 1992. 71(7): p. 1065-8.
59. Ross, D.J., et al., Lung allograft dysfunction correlates with gamma-interferon gene expression in bronchoalveolar lavage. J Heart Lung Transplant, 1999. 18(7): p. 627-36.
60. Wang, Y.L., et al., Influence of Th1, Th2, and Th3 cytokines during the early phase after liver transplantation. Transplant Proc, 2003. 35(8): p. 3024-5.
61. Wilkes, D.S., et al., Allogeneic bronchoalveolar lavage cells induce the histology of acute lung allograft rejection, and deposition of IgG2a in recipient murine lungs. J Immunol, 1995. 155(5): p. 2775-83.
62. Zuo, X.J., et al., Interleukin-12 mRNA levels in renal allograft fine-needle aspirates do not correlate with acute transplant rejection. Transplantation, 1995. 60(11): p. 1360-2.
63. Waaga, A.M., et al., Regulatory functions of self-restricted MHC class II allopeptide-specific Th2 clones in vivo. J Clin Invest, 2001. 107(7): p. 909-16.
64. Hayashi, S., et al., Adenovirus-mediated gene transfer of CTLA4Ig gene results in prolonged survival of heart allograft. Transpl Int, 2000. 13 Suppl 1: p. S329-32.
65. Lu, L., et al., Blockade of the CD40-CD40 ligand pathway potentiates the capacity of donor-derived dendritic cell progenitors to induce long-term cardiac allograft survival. Transplantation, 1997. 64(12): p. 1808-15.
66. Sayegh, M.H., et al., CD28-B7 blockade after alloantigenic challenge in vivo inhibits Th1 cytokines but spares Th2. J Exp Med, 1995. 181(5): p. 1869-74.
67. Tikkanen, J.M., K.B. Lemstrom, and P.K. Koskinen, Blockade of CD28/B7-2 costimulation inhibits experimental obliterative bronchiolitis in rat tracheal allografts: suppression of helper T cell type1-dominated immune response. Am J Respir Crit Care Med, 2002. 165(5): p. 724-9.
68. Xiao, Y., et al., CD28/B7-mediated costimulation is required for parathyroid gland allograft rejection in rats. Chin Med Sci J, 1999. 14(3): p. 158-62.
69. Vincenti, F., et al., Can antibody prophylaxis allow sparing of other immunosuppressives? Transplant Proc, 1999. 31(1-2): p. 1246-8.
70. Gorczynski, R.M., et al., Interleukin-13, in combination with anti-interleukin-12, increases graft prolongation after portal venous immunization with cultured allogeneic bone marrow-derived dendritic cells. Transplantation, 1996. 62(11): p. 1592-600.
71. Sun, Y., et al., TCR diversity in gammadeltaTCR+ hybridomas derived from mice given portal vein donor-specific pre-immunization and skin allografts. Immunol Lett, 1998. 64(2-3): p. 85-95.
72. Pirenne, J., et al., Regulatory cells, TH1/TH2 unbalance, and antibody-induced chronic rejection in operational tolerance induced by donor-specific blood transfusion. Transplantation, 2005. 79(3 Suppl): p. S25-7.
73. Shirwan, H., L. Barwari, and N.S. Khan, Predominant expression of T helper 2 cytokines and altered expression of T helper 1 cytokines in long-term allograft survival induced by intrathymic immune modulation with donor class I major histocompatibility complex peptides. Transplantation, 1998. 66(12): p. 1802-9.
74. Kishimoto, K., et al., Profile of cytokine production during the inhibition of acute xenograft rejection. Surg Today, 2000. 30(2): p. 159-62.
75. Li, X.C., et al., On histocompatibility barriers, Th1 to Th2 immune deviation, and the nature of the allograft responses. J Immunol, 1998. 161(5): p. 2241-7.
76. Koshiba, T., et al., Break of tolerance via donor-specific blood transfusion by high doses of steroids: a differential effect after intestinal transplantation and heart transplantation. Transplant Proc, 2003. 35(8): p. 3153-5.
77. Zand, M.S., et al., Interleukin-2 and interferon-gamma double knockout mice reject heterotopic cardiac allografts. Transplantation, 2000. 70(9): p. 1378-81.
78. Nathan, C., Nitric oxide as a secretory product of mammalian cells. Faseb J, 1992. 6(12): p. 3051-64.
79. Gourlay, W.A., et al., Resistance of established porcine islet xenografts to humoral rejection by hyperimmune sera. Transplantation, 1999. 68(6): p. 888-93.
80. Koshiba, T., et al., Regulatory cell-mediated tolerance does not protect against chronic rejection. Transplantation, 2003. 76(3): p. 588-96.
81. Nocera, A., et al., Cytokine mRNA expression in chronically rejected human renal allografts. Clin Transplant, 2004. 18(5): p. 564-70.
82. Le Moine, A., et al., Critical roles for IL-4, IL-5, and eosinophils in chronic skin allograft rejection. J Clin Invest, 1999. 103(12): p. 1659-67.
83. Mhoyan, A., et al., Predominant expression of the Th2 response in chronic cardiac allograft rejection. Transpl Int, 2003. 16(8): p. 464-73.
84. Shirwan, H., Chronic allograft rejection. Do the Th2 cells preferentially induced by indirect alloantigen recognition play a dominant role? Transplantation, 1999. 68(6): p. 715-26.
85. Kallio, E.A., et al., Blockade of complement inhibits obliterative bronchiolitis in rat tracheal allografts. Am J Respir Crit Care Med, 2000. 161(4 Pt 1): p. 1332-9.
86. Ganschow, R., et al., Th2 cytokine profile in infants predisposes to improved graft acceptance after liver transplantation. Transplantation, 2001. 72(5): p. 929-34.
87. Salter, R.D., et al., A binding site for the T-cell co-receptor CD8 on the alpha 3 domain of HLA-A2. Nature, 1990. 345(6270): p. 41-6.
88. von Boehmer, H., H.S. Teh, and P. Kisielow, The thymus selects the useful, neglects the useless and destroys the harmful. Immunol Today, 1989. 10(2): p. 57-61.
89. Krieger, N.R., D.P. Yin, and C.G. Fathman, CD4+ but not CD8+ cells are essential for allorejection. J Exp Med, 1996. 184(5): p. 2013-8.
90. Chai, J.G., et al., Regulatory T cells, derived from naive CD4+CD25- T cells by in vitro Foxp3 gene transfer, can induce transplantation tolerance. Transplantation, 2005. 79(10): p. 1310-6.
91. Graca, L., et al., Donor-specific transplantation tolerance: the paradoxical behavior of CD4+CD25+ T cells. Proc Natl Acad Sci U S A, 2004. 101(27): p. 10122-6.
92. Waldmann, H. and S. Cobbold, Exploiting tolerance processes in transplantation. Science, 2004. 305(5681): p. 209-12.
93. Walsh, P.T., D.K. Taylor, and L.A. Turka, Tregs and transplantation tolerance. J Clin Invest, 2004. 114(10): p. 1398-403.
94. Groux, H., Type 1 T-regulatory cells: their role in the control of immune responses. Transplantation, 2003. 75(9 Suppl): p. 8S-12S.
95. Battaglia, M., et al., Rapamycin and interleukin-10 treatment induces T regulatory type 1 cells that mediate antigen-specific transplantation tolerance. Diabetes, 2006. 55(1): p. 40-9.
96. Bahri, R., et al., Soluble HLA-G inhibits cell cycle progression in human alloreactive T lymphocytes. J Immunol, 2006. 176(3): p. 1331-9.
97. Le Rond, S., et al., Evidence to support the role of HLA-G5 in allograft acceptance through induction of immunosuppressive/ regulatory T cells. J Immunol, 2006. 176(5): p. 3266-76.
98. Rouas-Freiss, N., et al., Direct evidence to support the role of HLA-G in protecting the fetus from maternal uterine natural killer cytolysis. Proc Natl Acad Sci U S A, 1997. 94(21): p. 11520-5.
99. Fuzzi, B., et al., HLA-G expression in early embryos is a fundamental prerequisite for the obtainment of pregnancy. Eur J Immunol, 2002. 32(2): p. 311-5.
100. Noci, I., et al., Embryonic soluble HLA-G as a marker of developmental potential in embryos. Hum Reprod, 2005. 20(1): p. 138-46.
101. Sher, G., et al., Influence of early ICSI-derived embryo sHLA-G expression on pregnancy and implantation rates: a prospective study. Hum Reprod, 2005. 20(5): p. 1359-63.
102. Sher, G., et al., Expression of sHLA-G in supernatants of individually cultured 46-h embryos: a potentially valuable indicator of 'embryo competency' and IVF outcome. Reprod Biomed Online, 2004. 9(1): p. 74-8.
103. Rebmann, V., et al., Report of the Wet Workshop for Quantification of Soluble HLA-G in Essen, 2004. Hum Immunol, 2005. 66(8): p. 853-63.
104. Lila, N., et al., Human leukocyte antigen-G expression after heart transplantation is associated with a reduced incidence of rejection. Circulation, 2002. 105(16): p. 1949-54.
105. Lila, N., et al., Implication of HLA-G molecule in heart-graft acceptance. Lancet, 2000. 355(9221):p. 2138.
106. Qiu, J., et al., Soluble HLA-G expression and renal graft acceptance. Am J Transplant, 2006. 6(9): p. 2152-6.
107. Creput, C., et al., Incidence of renal and liver rejection and patient survival rate following combined liver and kidney transplantation. Am J Transplant, 2003. 3(3): p. 348-56.
108. Creput, C., et al., Human leukocyte antigen-G (HLA-G) expression in biliary epithelial cells is associated with allograft acceptance in liver-kidney transplantation. J Hepatol, 2003. 39(4): p. 587-94.
109. Le Rond, S., et al., Alloreactive CD4+ and CD8+ T cells express the immunotolerant HLA-G molecule in mixed lymphocyte reactions: in vivo implications in transplanted patients. Eur J Immunol, 2004. 34(3): p. 649-60.
110. Lila, N., et al., Soluble HLA-G protein secreted by allo-specific CD4+ T cells suppresses the allo-proliferative response: a CD4+ T cell regulatory mechanism. Proc Natl Acad Sci U S A, 2001. 98(21): p. 12150-5.
2. Ishitani, A. and D.E. Geraghty, Alternative splicing of HLA-G transcripts yields proteins with primary structures resembling both class I and class II antigens. Proc Natl Acad Sci U S A, 1992. 89(9): p. 3947-51.
3. Kirszenbaum, M., et al., An alternatively spliced form of HLA-G mRNA in human trophoblasts and evidence for the presence of HLA-G transcript in adult lymphocytes. Proc Natl Acad Sci U S A, 1994. 91(10): p. 4209-13.
4. Kovats, S., et al., A class I antigen, HLA-G, expressed in human trophoblasts. Science, 1990. 248(4952): p. 220-3.
5. Moreau, P., et al., Soluble HLA-G molecule. An alternatively spliced HLA-G mRNA form candidate to encode it in peripheral blood mononuclear cells and human trophoblasts. Hum Immunol, 1995. 43(3): p. 231-6.
6. Paul, P., et al., Identification of HLA-G7 as a new splice variant of the HLA-G mRNA and expression of soluble HLA-G5, -G6, and -G7 transcripts in human transfected cells. Hum Immunol, 2000. 61(11): p. 1138-49.
7. Creput, C., et al., Human leukocyte antigen-G (HLA-G) expression in biliary epithelial cells is associated with allograft acceptance in liver-kidney transplantation. J Hepatol, 2003. 39(4): p. 587-94.
8. Creput, C., et al., Detection of HLA-G in serum and graft biopsy associated with fewer acute rejections following combined liver-kidney transplantation: possible implications for monitoring patients. Hum Immunol, 2003. 64(11): p. 1033-8.
9. Le Rond, S., et al., Evidence to support the role of HLA-G5 in allograft acceptance through induction of immunosuppressive/ regulatory T cells. J Immunol, 2006. 176(5): p. 3266-76.
10. Le Rond, S., et al., Alloreactive CD4+ and CD8+ T cells express the immunotolerant HLA-G molecule in mixed lymphocyte reactions: in vivo implications in transplanted patients. Eur J Immunol, 2004. 34(3): p. 649-60.
11. Lila, N., et al., Human leukocyte antigen-G expression after heart transplantation is associated with areduced incidence of rejection. Circulation, 2002. 105(16): p. 1949-54.
12. Lila, N., et al., Implication of HLA-G molecule in heart-graft acceptance. Lancet, 2000. 355(9221): p. 2138.
13. Luque, J., et al., Soluble HLA-G in heart transplantation: their relationship to rejection episodes and immunosuppressive therapy. Hum Immunol, 2006. 67(4-5): p. 257-63.
14. Qiu, J., et al., Soluble HLA-G expression and renal graft acceptance. Am J Transplant, 2006. 6(9): p. 2152-6.
15. Colonna, M., et al., A common inhibitory receptor for major histocompatibility complex class I molecules on human lymphoid and myelomonocytic cells. J Exp Med, 1997. 186(11): p. 1809-18.
16. Colonna, M., et al., Human myelomonocytic cells express an inhibitory receptor for classical and nonclassical MHC class I molecules. J Immunol, 1998. 160(7): p. 3096-100.
17. Cosman, D., et al., A novel immunoglobulin superfamily receptor for cellular and viral MHC class I molecules. Immunity, 1997. 7(2): p. 273-82.
18. Ponte, M., et al., Inhibitory receptors sensing HLA-G1 molecules in pregnancy: decidua-associated natural killer cells express LIR-1 and CD94/NKG2A and acquire p49, an HLA-G1-specific receptor. Proc Natl Acad Sci U S A, 1999. 96(10): p. 5674-9.
19. Rajagopalan, S. and E.O. Long, A human histocompatibility leukocyte antigen (HLA)-G-specific receptor expressed on all natural killer cells. J Exp Med, 1999. 189(7): p. 1093-100.
20. Shiroishi, M., et al., Human inhibitory receptors Ig-like transcript 2 (ILT2) and ILT4 compete with CD8 for MHC class I binding and bind preferentially to HLA-G. Proc Natl Acad Sci U S A, 2003. 100(15): p. 8856-61.
21. Apps, R., et al., A homodimeric complex of HLA-G on normal trophoblast cells modulates antigen-presenting cells via LILRB1. Eur J Immunol, 2007. 37(7): p. 1924-37.
22. Boyson, J.E., et al., Disulfide bond-mediated dimerization of HLA-G on the cell surface. Proc Natl Acad Sci U S A, 2002. 99(25): p. 16180-5.
23. Gonen-Gross, T., et al., Complexes of HLA-G protein on the cell surface are important for leukocyte Ig-like receptor-1 function. J Immunol, 2003. 171(3): p. 1343-51.
24. Gonen-Gross, T., et al., Special organization of the HLA-G protein on the cell surface. Hum Immunol,2003. 64(11): p. 1011-6.
25. Shiroishi, M., D. Kohda, and K. Maenaka, Preparation and crystallization of the disulfide-linked HLA-G dimer. Biochim Biophys Acta, 2006. 1764(5): p. 985-8.
26. Shiroishi, M., et al., Efficient leukocyte Ig-like receptor signaling and crystal structure of disulfide-linked HLA-G dimer. J Biol Chem, 2006. 281(15): p. 10439-47.
27. Hu, H.M., et al., Immunological monitoring of patients with melanoma after peptide vaccination using soluble peptide/HLA-A2 dimer complexes. J Immunother (1997), 2004. 27(1): p. 48-59.
28. Wang, Y.D. and W.F. Chen, Detecting specific cytotoxic T lymphocytes against SARS-coronavirus with DimerX HLA-A2:Ig fusion protein. Clin Immunol, 2004. 113(2): p. 151-4.
29. Weng, X., et al., Peptide-dependent inhibition of alloreactive T-cell response by soluble divalent HLA-A2/IgG molecule in vitro. Transplantation, 2007. 84(10): p. 1298-306.
30. Burlingham, W.J., S.S. Ceman, and R. DeMars, Secretion and cell surface expression of IgG1 are impaired in human B lymphoblasts that lack HLA-A, -B, and -C antigens. Proc Natl Acad Sci U S A, 1989. 86(20): p. 8005-9.
31. Solheim, J.C., et al., Prominence of beta 2-microglobulin, class I heavy chain conformation, and tapasin in the interactions of class I heavy chain with calreticulin and the transporter associated with antigen processing. J Immunol, 1997. 158(5): p. 2236-41.
32.房崇芸,吴雄文,龚非力.可溶性人类白细胞抗原-G1 cDNA的克隆及序列分析.免疫学杂志, 2001. 17: p. 81-84.
33.陈浩,翁秀芳,吴雄文等.人β2m基因的克隆及表达.华中科技大学学报(医学版), 2004. 33(1): p. 1-4.
34.杨敬宁,吴雄文,梁智辉等.可溶性HLA-G1重链分子的构建、表达及纯化.中国免疫学杂志, 2005. 21(4): p. 287-290.
35. Ladasky, J.J., et al., Residue 3 of beta2-microglobulin affects binding of class I MHC molecules by the W6/32 antibody. Immunogenetics, 1999. 49(4): p. 312-20.
36. Tran, T.M., et al., The epitope recognized by pan-HLA class I-reactive monoclonal antibody W6/32 and its relationship to unusual stability of the HLA-B27/beta2-microglobulin complex. Immunogenetics, 2001. 53(6): p. 440-6.
37. Allan, D.S., et al., Tetrameric complexes of HLA-E, HLA-F, and HLA-G. J Immunol Methods, 2002. 268(1): p. 43-50.
38.吴雄文,梁智辉.实用免疫学实验技术.湖北科学技术出版社, 2001.
39. Demaria, S., et al., Soluble beta 2-microglobulin-free class I heavy chains are released from the surface of activated and leukemia cells by a metalloprotease. J Biol Chem, 1994. 269(9): p. 6689-94.
40. Dong, Y., et al., Soluble nonclassical HLA generated by the metalloproteinase pathway. Hum Immunol, 2003. 64(8): p. 802-10.
41. Park, G.M., et al., Soluble HLA-G generated by proteolytic shedding inhibits NK-mediated cell lysis. Biochem Biophys Res Commun, 2004. 313(3): p. 606-11.
42. Blaschitz, A., et al., The soluble pool of HLA-G produced by human trophoblasts does not include detectable levels of the intron 4-containing HLA-G5 and HLA-G6 isoforms. Mol Hum Reprod, 2005. 11(10): p. 699-710.
43. Salter RD, Howell DN, Cresswell P. Genes regulating HLA class I antigen expression in T-B lymphoblast hybrids. Immunogenetics 1985;21(3):235-246.
44. Bunce M, O'Neill CM, Barnardo MC, Krausa P, Browning MJ, Morris PJ et al. Phototyping: comprehensive DNA typing for HLA-A, B, C, DRB1, DRB3, DRB4, DRB5 & DQB1 by PCR with 144 primer mixes utilizing sequence-specific primers (PCR-SSP). Tissue Antigens 1995;46(5):355-367.
45. Hoefel D ,Grooby WL ,Monis PT,et al. A comparative study of carboxyfluorescein diacetate and carboxyfluorescein diacetate succinimidyl ester as indicators of bacterial activity. J Microbiol Methods, 2003, 52 :379-88.
46. AnguloR, Fulcher DA.Measurement of Candida-specifc blastogenesis :comparison of carboxyfluorescein succinimidyl ester labelling of T cells, thymidine incorporation , and CD69 expression. Cytometry, 1998, 34 :143-51.
47. Fulcher, D., Wong, S.,.Carboxyfluorescein succinimidyl ester-based proliferative assays for assessment of T-cell function in the diagnostic laboratory. Immunol. Cell Biol. 1999, 77:559.
48. Popma, S.H., Krasinskas, A.M., McLean, A.D., et al. Immune monitoring in xenotransplantation: the multiparameter flow cytometric mixed lymphocyte culture assay. Cytometry 2000. 42:277.
49. Babusikova, O., et al., Flow cytometric analysis of some activation/proliferation markers on humanthymocytes and their correlation with cell proliferation. Neoplasma, 1999. 46(6): p. 349-55.
50.Singal, D.P., Quantitative studies of alloantigen-reactive human lymphocytes in primary and secondary MLC. Hum Immunol, 1980. 1(1): p. 67-76.
51. Korzeniewski, C. and D.M. Callewaert, An enzyme-release assay for natural cytotoxicity. J Immunol Methods, 1983. 64(3): p. 313-20.
52. Reutelingsperger, C.P. and W.L. van Heerde, Annexin V, the regulator of phosphatidylserine-catalyzed inflammation and coagulation during apoptosis. Cell Mol Life Sci, 1997. 53(6): p. 527-32.
53. Rebmann, V., et al., Detection of HLA-G5 secreting cells. Hum Immunol, 2003. 64(11): p. 1017-24.
54. Kapasi, K., et al., HLA-G has a concentration-dependent effect on the generation of an allo-CTL response. Immunology, 2000. 101(2): p. 191-200.
55. Marchal-Bras-Goncalves, R., et al., A soluble HLA-G protein that inhibits natural killer cell-mediated cytotoxicity. Transplant Proc, 2001. 33(3): p. 2355-9.
56. Bainbridge, D.R., S.A. Ellis, and I.L. Sargent, HLA-G suppresses proliferation of CD4(+) T-lymphocytes. J Reprod Immunol, 2000. 48(1): p. 17-26.
57. Bahri, R., et al., Soluble HLA-G inhibits cell cycle progression in human alloreactive T lymphocytes. J Immunol, 2006. 176(3): p. 1331-9.
58. Feger, U., et al., HLA-G expression defines a novel regulatory T-cell subset present in human peripheral blood and sites of inflammation. Blood, 2007. 110(2): p. 568-77.
59. Contini, P., et al., Soluble HLA-A,-B,-C and -G molecules induce apoptosis in T and NK CD8+ cells and inhibit cytotoxic T cell activity through CD8 ligation. Eur J Immunol, 2003. 33(1): p. 125-34.
60. Fournel, S., et al., Cutting edge: soluble HLA-G1 triggers CD95/CD95 ligand-mediated apoptosis in activated CD8+ cells by interacting with CD8. J Immunol, 2000. 164(12): p. 6100-4.
61. Kanai, T., et al., A subclass of soluble HLA-G1 modulates the release of cytokines from mononuclear cells present in the decidua additively to membrane-bound HLA-G1. J Reprod Immunol, 2003. 60(2): p. 85-96.
62. Kanai, T., et al., Soluble HLA-G influences the release of cytokines from allogeneic peripheral blood mononuclear cells in culture. Mol Hum Reprod, 2001. 7(2): p. 195-200.
63. Poulton, T.A., et al., Changes in activation markers and cell membrane receptors on human peripheralblood T lymphocytes during cell cycle progression after PHA stimulation. Immunology, 1988. 64(3): p. 419-25.
64. Johannisson, A., et al., Effects of four trichothecene mycotoxins on activation marker expression and cell proliferation of human lymphocytes in culture. Cell Biol Toxicol, 1999. 15(4): p. 203-15.
65. Borges, L., et al., A family of human lymphoid and myeloid Ig-like receptors, some of which bind to MHC class I molecules. J Immunol, 1997. 159(11): p. 5192-6.
66. Cosman, D., N. Fanger, and L. Borges, Human cytomegalovirus, MHC class I and inhibitory signalling receptors: more questions than answers. Immunol Rev, 1999. 168: p. 177-85.
67. LeMaoult, J., et al., HLA-G up-regulates ILT2, ILT3, ILT4, and KIR2DL4 in antigen presenting cells, NK cells, and T cells. Faseb J, 2005. 19(6): p. 662-4.
1. Doherty, P.C. and R.M. Zinkernagel, A biological role for the major histocompatibility antigens. Lancet, 1975. 1(7922): p. 1406-9.
2. Svejgaard, A., P. Platz, and L.P. Ryder, HLA and disease 1982--a survey. Immunol Rev, 1983. 70: p. 193-218.
3. Ellis, S.A., M.S. Palmer, and A.J. McMichael, Human trophoblast and the choriocarcinoma cell lineBeWo express a truncated HLA Class I molecule. J Immunol, 1990. 144(2): p. 731-5.
4. Geraghty, D.E., B.H. Koller, and H.T. Orr, A human major histocompatibility complex class I gene that encodes a protein with a shortened cytoplasmic segment. Proc Natl Acad Sci U S A, 1987. 84(24): p. 9145-9.
5. Redman, C.W., et al., Class 1 major histocompatibility complex antigens on human extra-villous trophoblast. Immunology, 1984. 52(3): p. 457-68.
6. Schmidt, C.M. and H.T. Orr, A physical linkage map of HLA-A, -G, -7.5p, and -F. Hum Immunol, 1991. 31(3): p. 180-5.
7. Carosella, E.D., J. Dausset, and N. Rouas-Freiss, Immunotolerant functions of HLA-G. Cell Mol Life Sci, 1999. 55(3): p. 327-33.
8. Ishitani, A., et al., Protein expression and peptide binding suggest unique and interacting functional roles for HLA-E, F, and G in maternal-placental immune recognition. J Immunol, 2003. 171(3): p. 1376-84.
9. LeMaoult, J., et al., HLA-G1-expressing antigen-presenting cells induce immunosuppressive CD4+ T cells. Proc Natl Acad Sci U S A, 2004. 101(18): p. 7064-9.
10. Le Gal, F.A., et al., HLA-G-mediated inhibition of antigen-specific cytotoxic T lymphocytes. Int Immunol, 1999. 11(8): p. 1351-6.
11. Contini, P., et al., Soluble HLA-A,-B,-C and -G molecules induce apoptosis in T and NK CD8+ cells and inhibit cytotoxic T cell activity through CD8 ligation. Eur J Immunol, 2003. 33(1): p. 125-34.
12. Fournel, S., et al., Cutting edge: soluble HLA-G1 triggers CD95/CD95 ligand-mediated apoptosis in activated CD8+ cells by interacting with CD8. J Immunol, 2000. 164(12): p. 6100-4.
13. Messer, G., et al., HLA-J, a second inactivated class I HLA gene related to HLA-G and HLA-A. Implications for the evolution of the HLA-A-related genes. J Immunol, 1992. 148(12): p. 4043-53.
14. Heinrichs, H. and H.T. Orr, HLA non-A,B,C class I genes: their structure and expression. Immunol Res, 1990. 9(4): p. 265-74.
15. Davis, D.M., et al., Impaired spontaneous endocytosis of HLA-G. Eur J Immunol, 1997. 27(10): p. 2714-9.
16. Lee, N., et al., HLA-E is a major ligand for the natural killer inhibitory receptor CD94/NKG2A.Proc Natl Acad Sci U S A, 1998. 95(9): p. 5199-204.
17. Llano, M., et al., HLA-E-bound peptides influence recognition by inhibitory and triggering CD94/NKG2 receptors: preferential response to an HLA-G-derived nonamer. Eur J Immunol, 1998. 28(9): p. 2854-63.
18. He, X., et al., Identification of a novel HLA-F allele - HLA-F*010102. Tissue Antigens, 2004. 63(2): p. 181-3.
19. Ellis, S.A., et al., Evidence for a novel HLA antigen found on human extravillous trophoblast and a choriocarcinoma cell line. Immunology, 1986. 59(4): p. 595-601.
20. Ishitani, A. and D.E. Geraghty, Alternative splicing of HLA-G transcripts yields proteins with primary structures resembling both class I and class II antigens. Proc Natl Acad Sci U S A, 1992. 89(9): p. 3947-51.
21. Kirszenbaum, M., et al., An alternatively spliced form of HLA-G mRNA in human trophoblasts and evidence for the presence of HLA-G transcript in adult lymphocytes. Proc Natl Acad Sci U S A, 1994. 91(10): p. 4209-13.
22. Fujii, T., A. Ishitani, and D.E. Geraghty, A soluble form of the HLA-G antigen is encoded by a messenger ribonucleic acid containing intron 4. J Immunol, 1994. 153(12): p. 5516-24.
23. Blaschitz, A., et al., Endothelial cells in chorionic fetal vessels of first trimester placenta express HLA-G. Eur J Immunol, 1997. 27(12): p. 3380-8.
24. Crisa, L., et al., Identification of a thymic epithelial cell subset sharing expression of the class Ib HLA-G molecule with fetal trophoblasts. J Exp Med, 1997. 186(2): p. 289-98.
25. Hunt, J.S., et al., HLA-G and immune tolerance in pregnancy. Faseb J, 2005. 19(7): p. 681-93.
26. McMaster, M., et al., HLA-G isoforms produced by placental cytotrophoblasts and found in amniotic fluid are due to unusual glycosylation. J Immunol, 1998. 160(12): p. 5922-8.
27. Yang, Y., et al., Expression of HLA-G in human mononuclear phagocytes and selective induction by IFN-gamma. J Immunol, 1996. 156(11): p. 4224-31.
28. Parham, P., et al., Nature of polymorphism in HLA-A, -B, and -C molecules. Proc Natl Acad Sci U S A, 1988. 85(11): p. 4005-9.
29. Shimizu, Y., et al., Transfer and expression of three cloned human non-HLA-A,B,C class I majorhistocompatibility complex genes in mutant lymphoblastoid cells. Proc Natl Acad Sci U S A, 1988. 85(1): p. 227-31.
30. Dobbe, L.M., et al., Biochemical complexity of serum HLA class I molecules. Immunogenetics, 1988. 27(3): p. 203-10.
31. Paul, P., et al., Identification of HLA-G7 as a new splice variant of the HLA-G mRNA and expression of soluble HLA-G5, -G6, and -G7 transcripts in human transfected cells. Hum Immunol, 2000. 61(11): p. 1138-49.
32. Clements, C.S., et al., Crystal structure of HLA-G: a nonclassical MHC class I molecule expressed at the fetal-maternal interface. Proc Natl Acad Sci U S A, 2005. 102(9): p. 3360-5.
33. Lee, N., et al., The membrane-bound and soluble forms of HLA-G bind identical sets of endogenous peptides but differ with respect to TAP association. Immunity, 1995. 3(5): p. 591-600.
34. Diehl, M., et al., Nonclassical HLA-G molecules are classical peptide presenters. Curr Biol, 1996. 6(3): p. 305-14.
35. Munz, C., S. Stevanovic, and H.G. Rammensee, Peptide presentation and NK inhibition by HLA-G. J Reprod Immunol, 1999. 43(2): p. 139-55.
36. Boyson, J.E., et al., Disulfide bond-mediated dimerization of HLA-G on the cell surface. Proc Natl Acad Sci U S A, 2002. 99(25): p. 16180-5.
37. He, X., et al., Promiscuous antigen presentation by the nonclassical MHC Ib Qa-2 is enabled by a shallow, hydrophobic groove and self-stabilized peptide conformation. Structure, 2001. 9(12): p. 1213-24.
38. Khan, A.R., et al., The structure and stability of an HLA-A*0201/octameric tax peptide complex with an empty conserved peptide-N-terminal binding site. J Immunol, 2000. 164(12): p. 6398-405.
39. Strong, R.K., et al., HLA-E allelic variants. Correlating differential expression, peptide affinities, crystal structures, and thermal stabilities. J Biol Chem, 2003. 278(7): p. 5082-90.
40. Clements, C.S., et al., The production, purification and crystallization of a soluble form of the nonclassical MHC HLA-G: the essential role of cobalt. Acta Crystallogr Sect F Struct Biol Cryst Commun, 2006. 62(Pt 1): p. 70-3.
41. Shiroishi, M., D. Kohda, and K. Maenaka, Preparation and crystallization of the disulfide-linkedHLA-G dimer. Biochim Biophys Acta, 2006. 1764(5): p. 985-8.
42. Gonen-Gross, T., et al., Complexes of HLA-G protein on the cell surface are important for leukocyte Ig-like receptor-1 function. J Immunol, 2003. 171(3): p. 1343-51.
43. Gonen-Gross, T., et al., Special organization of the HLA-G protein on the cell surface. Hum Immunol, 2003. 64(11): p. 1011-6.
44. Morales, P.J., et al., Placental cell expression of HLA-G2 isoforms is limited to the invasive trophoblast phenotype. J Immunol, 2003. 171(11): p. 6215-24.
45. Shiroishi, M., et al., Efficient leukocyte Ig-like receptor signaling and crystal structure of disulfide-linked HLA-G dimer. J Biol Chem, 2006. 281(15): p. 10439-47.
46. Brown, D., J. Trowsdale, and R. Allen, The LILR family: modulators of innate and adaptive immune pathways in health and disease. Tissue Antigens, 2004. 64(3): p. 215-25.
47. Chapman, T.L., A.P. Heikeman, and P.J. Bjorkman, The inhibitory receptor LIR-1 uses a common binding interaction to recognize class I MHC molecules and the viral homolog UL18. Immunity, 1999. 11(5): p. 603-13.
48. Willcox, B.E., L.M. Thomas, and P.J. Bjorkman, Crystal structure of HLA-A2 bound to LIR-1, a host and viral major histocompatibility complex receptor. Nat Immunol, 2003. 4(9): p. 913-9.
49. Shiroishi, M., et al., Human inhibitory receptors Ig-like transcript 2 (ILT2) and ILT4 compete with CD8 for MHC class I binding and bind preferentially to HLA-G. Proc Natl Acad Sci U S A, 2003. 100(15): p. 8856-61.
50. Ponte, M., et al., Inhibitory receptors sensing HLA-G1 molecules in pregnancy: decidua-associated natural killer cells express LIR-1 and CD94/NKG2A and acquire p49, an HLA-G1-specific receptor. Proc Natl Acad Sci U S A, 1999. 96(10): p. 5674-9.
51. Rajagopalan, S. and E.O. Long, A human histocompatibility leukocyte antigen (HLA)-G-specific receptor expressed on all natural killer cells. J Exp Med, 1999. 189(7): p. 1093-100.
52. Rajagopalan, S., et al., Activation of NK cells by an endocytosed receptor for soluble HLA-G. PLoS Biol, 2006. 4(1): p. e9.
53. Yan, W.H. and L.A. Fan, Residues Met76 and Gln79 in HLA-G alpha1 domain involve in KIR2DL4 recognition. Cell Res, 2005. 15(3): p. 176-82.
54. Boyington, J.C., et al., Crystal structure of an NK cell immunoglobulin-like receptor in complex with its class I MHC ligand. Nature, 2000. 405(6786): p. 537-43.
55. Fan, Q.R., E.O. Long, and D.C. Wiley, Crystal structure of the human natural killer cell inhibitory receptor KIR2DL1-HLA-Cw4 complex. Nat Immunol, 2001. 2(5): p. 452-60.
56. Benichou, G., A. Valujskikh, and P.S. Heeger, Contributions of direct and indirect T cell alloreactivity during allograft rejection in mice. J Immunol, 1999. 162(1): p. 352-8.
57. Sayegh, M.H. and C.B. Carpenter, Role of indirect allorecognition in allograft rejection. Int Rev Immunol, 1996. 13(3): p. 221-9.
58. Schwartz, R.H., Costimulation of T lymphocytes: the role of CD28, CTLA-4, and B7/BB1 in interleukin-2 production and immunotherapy. Cell, 1992. 71(7): p. 1065-8.
59. Ross, D.J., et al., Lung allograft dysfunction correlates with gamma-interferon gene expression in bronchoalveolar lavage. J Heart Lung Transplant, 1999. 18(7): p. 627-36.
60. Wang, Y.L., et al., Influence of Th1, Th2, and Th3 cytokines during the early phase after liver transplantation. Transplant Proc, 2003. 35(8): p. 3024-5.
61. Wilkes, D.S., et al., Allogeneic bronchoalveolar lavage cells induce the histology of acute lung allograft rejection, and deposition of IgG2a in recipient murine lungs. J Immunol, 1995. 155(5): p. 2775-83.
62. Zuo, X.J., et al., Interleukin-12 mRNA levels in renal allograft fine-needle aspirates do not correlate with acute transplant rejection. Transplantation, 1995. 60(11): p. 1360-2.
63. Waaga, A.M., et al., Regulatory functions of self-restricted MHC class II allopeptide-specific Th2 clones in vivo. J Clin Invest, 2001. 107(7): p. 909-16.
64. Hayashi, S., et al., Adenovirus-mediated gene transfer of CTLA4Ig gene results in prolonged survival of heart allograft. Transpl Int, 2000. 13 Suppl 1: p. S329-32.
65. Lu, L., et al., Blockade of the CD40-CD40 ligand pathway potentiates the capacity of donor-derived dendritic cell progenitors to induce long-term cardiac allograft survival. Transplantation, 1997. 64(12): p. 1808-15.
66. Sayegh, M.H., et al., CD28-B7 blockade after alloantigenic challenge in vivo inhibits Th1 cytokines but spares Th2. J Exp Med, 1995. 181(5): p. 1869-74.
67. Tikkanen, J.M., K.B. Lemstrom, and P.K. Koskinen, Blockade of CD28/B7-2 costimulation inhibits experimental obliterative bronchiolitis in rat tracheal allografts: suppression of helper T cell type1-dominated immune response. Am J Respir Crit Care Med, 2002. 165(5): p. 724-9.
68. Xiao, Y., et al., CD28/B7-mediated costimulation is required for parathyroid gland allograft rejection in rats. Chin Med Sci J, 1999. 14(3): p. 158-62.
69. Vincenti, F., et al., Can antibody prophylaxis allow sparing of other immunosuppressives? Transplant Proc, 1999. 31(1-2): p. 1246-8.
70. Gorczynski, R.M., et al., Interleukin-13, in combination with anti-interleukin-12, increases graft prolongation after portal venous immunization with cultured allogeneic bone marrow-derived dendritic cells. Transplantation, 1996. 62(11): p. 1592-600.
71. Sun, Y., et al., TCR diversity in gammadeltaTCR+ hybridomas derived from mice given portal vein donor-specific pre-immunization and skin allografts. Immunol Lett, 1998. 64(2-3): p. 85-95.
72. Pirenne, J., et al., Regulatory cells, TH1/TH2 unbalance, and antibody-induced chronic rejection in operational tolerance induced by donor-specific blood transfusion. Transplantation, 2005. 79(3 Suppl): p. S25-7.
73. Shirwan, H., L. Barwari, and N.S. Khan, Predominant expression of T helper 2 cytokines and altered expression of T helper 1 cytokines in long-term allograft survival induced by intrathymic immune modulation with donor class I major histocompatibility complex peptides. Transplantation, 1998. 66(12): p. 1802-9.
74. Kishimoto, K., et al., Profile of cytokine production during the inhibition of acute xenograft rejection. Surg Today, 2000. 30(2): p. 159-62.
75. Li, X.C., et al., On histocompatibility barriers, Th1 to Th2 immune deviation, and the nature of the allograft responses. J Immunol, 1998. 161(5): p. 2241-7.
76. Koshiba, T., et al., Break of tolerance via donor-specific blood transfusion by high doses of steroids: a differential effect after intestinal transplantation and heart transplantation. Transplant Proc, 2003. 35(8): p. 3153-5.
77. Zand, M.S., et al., Interleukin-2 and interferon-gamma double knockout mice reject heterotopic cardiac allografts. Transplantation, 2000. 70(9): p. 1378-81.
78. Nathan, C., Nitric oxide as a secretory product of mammalian cells. Faseb J, 1992. 6(12): p. 3051-64.
79. Gourlay, W.A., et al., Resistance of established porcine islet xenografts to humoral rejection by hyperimmune sera. Transplantation, 1999. 68(6): p. 888-93.
80. Koshiba, T., et al., Regulatory cell-mediated tolerance does not protect against chronic rejection. Transplantation, 2003. 76(3): p. 588-96.
81. Nocera, A., et al., Cytokine mRNA expression in chronically rejected human renal allografts. Clin Transplant, 2004. 18(5): p. 564-70.
82. Le Moine, A., et al., Critical roles for IL-4, IL-5, and eosinophils in chronic skin allograft rejection. J Clin Invest, 1999. 103(12): p. 1659-67.
83. Mhoyan, A., et al., Predominant expression of the Th2 response in chronic cardiac allograft rejection. Transpl Int, 2003. 16(8): p. 464-73.
84. Shirwan, H., Chronic allograft rejection. Do the Th2 cells preferentially induced by indirect alloantigen recognition play a dominant role? Transplantation, 1999. 68(6): p. 715-26.
85. Kallio, E.A., et al., Blockade of complement inhibits obliterative bronchiolitis in rat tracheal allografts. Am J Respir Crit Care Med, 2000. 161(4 Pt 1): p. 1332-9.
86. Ganschow, R., et al., Th2 cytokine profile in infants predisposes to improved graft acceptance after liver transplantation. Transplantation, 2001. 72(5): p. 929-34.
87. Salter, R.D., et al., A binding site for the T-cell co-receptor CD8 on the alpha 3 domain of HLA-A2. Nature, 1990. 345(6270): p. 41-6.
88. von Boehmer, H., H.S. Teh, and P. Kisielow, The thymus selects the useful, neglects the useless and destroys the harmful. Immunol Today, 1989. 10(2): p. 57-61.
89. Krieger, N.R., D.P. Yin, and C.G. Fathman, CD4+ but not CD8+ cells are essential for allorejection. J Exp Med, 1996. 184(5): p. 2013-8.
90. Chai, J.G., et al., Regulatory T cells, derived from naive CD4+CD25- T cells by in vitro Foxp3 gene transfer, can induce transplantation tolerance. Transplantation, 2005. 79(10): p. 1310-6.
91. Graca, L., et al., Donor-specific transplantation tolerance: the paradoxical behavior of CD4+CD25+ T cells. Proc Natl Acad Sci U S A, 2004. 101(27): p. 10122-6.
92. Waldmann, H. and S. Cobbold, Exploiting tolerance processes in transplantation. Science, 2004. 305(5681): p. 209-12.
93. Walsh, P.T., D.K. Taylor, and L.A. Turka, Tregs and transplantation tolerance. J Clin Invest, 2004. 114(10): p. 1398-403.
94. Groux, H., Type 1 T-regulatory cells: their role in the control of immune responses. Transplantation, 2003. 75(9 Suppl): p. 8S-12S.
95. Battaglia, M., et al., Rapamycin and interleukin-10 treatment induces T regulatory type 1 cells that mediate antigen-specific transplantation tolerance. Diabetes, 2006. 55(1): p. 40-9.
96. Bahri, R., et al., Soluble HLA-G inhibits cell cycle progression in human alloreactive T lymphocytes. J Immunol, 2006. 176(3): p. 1331-9.
97. Le Rond, S., et al., Evidence to support the role of HLA-G5 in allograft acceptance through induction of immunosuppressive/ regulatory T cells. J Immunol, 2006. 176(5): p. 3266-76.
98. Rouas-Freiss, N., et al., Direct evidence to support the role of HLA-G in protecting the fetus from maternal uterine natural killer cytolysis. Proc Natl Acad Sci U S A, 1997. 94(21): p. 11520-5.
99. Fuzzi, B., et al., HLA-G expression in early embryos is a fundamental prerequisite for the obtainment of pregnancy. Eur J Immunol, 2002. 32(2): p. 311-5.
100. Noci, I., et al., Embryonic soluble HLA-G as a marker of developmental potential in embryos. Hum Reprod, 2005. 20(1): p. 138-46.
101. Sher, G., et al., Influence of early ICSI-derived embryo sHLA-G expression on pregnancy and implantation rates: a prospective study. Hum Reprod, 2005. 20(5): p. 1359-63.
102. Sher, G., et al., Expression of sHLA-G in supernatants of individually cultured 46-h embryos: a potentially valuable indicator of 'embryo competency' and IVF outcome. Reprod Biomed Online, 2004. 9(1): p. 74-8.
103. Rebmann, V., et al., Report of the Wet Workshop for Quantification of Soluble HLA-G in Essen, 2004. Hum Immunol, 2005. 66(8): p. 853-63.
104. Lila, N., et al., Human leukocyte antigen-G expression after heart transplantation is associated with a reduced incidence of rejection. Circulation, 2002. 105(16): p. 1949-54.
105. Lila, N., et al., Implication of HLA-G molecule in heart-graft acceptance. Lancet, 2000. 355(9221):p. 2138.
106. Qiu, J., et al., Soluble HLA-G expression and renal graft acceptance. Am J Transplant, 2006. 6(9): p. 2152-6.
107. Creput, C., et al., Incidence of renal and liver rejection and patient survival rate following combined liver and kidney transplantation. Am J Transplant, 2003. 3(3): p. 348-56.
108. Creput, C., et al., Human leukocyte antigen-G (HLA-G) expression in biliary epithelial cells is associated with allograft acceptance in liver-kidney transplantation. J Hepatol, 2003. 39(4): p. 587-94.
109. Le Rond, S., et al., Alloreactive CD4+ and CD8+ T cells express the immunotolerant HLA-G molecule in mixed lymphocyte reactions: in vivo implications in transplanted patients. Eur J Immunol, 2004. 34(3): p. 649-60.
110. Lila, N., et al., Soluble HLA-G protein secreted by allo-specific CD4+ T cells suppresses the allo-proliferative response: a CD4+ T cell regulatory mechanism. Proc Natl Acad Sci U S A, 2001. 98(21): p. 12150-5.