CD38~+/~-HLA-DR~+CD8~+T淋巴细胞比例与HIV/AIDS病人免疫状态的关系
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摘要
目的分析不同CD4+T淋巴细胞(简称CD4细胞)计数,血浆病毒载量(VL)水平下,艾滋病病毒(HIV)感染者/艾滋病(AIDS)病人(简称HIV/AIDS病人)CD38~+/~-HLA-DR~+CD8~+T细胞比例变化,及其与CD8+T淋巴细胞(简称CD8细胞)计数的相关性,探究CD38~+/~-HLA-DR~+CD8~+T细胞比例与HIV/AIDS病人免疫状态间的关系。方法对46例HIV/AIDS病人外周血单个核细胞进行流式染色,检测CD38~+/~-HLA-DR~+CD8~+T细胞比例。结果1)CD4细胞分组:CD4细胞<200个/μL者,CD38-HLA-DR+CD8+T细胞比例升高(P=0.02),CD38+HLA-DR+CD8+T细胞比例两组间无统计学差异(P>0.05);CD4细胞>200个/μL者,CD38-HLA-DR+CD8+T细胞比例与CD8细胞计数正性相关(r=0.36,P=0.04)。2)VL分组:两组病人CD38~+/~-HLA-DR~+CD8~+T细胞比例无统计学差异(P>0.05),且均与CD8细胞计数无相关性(P>0.05)。结论HIV/AIDS病人CD8细胞活化水平升高,与CD38+HLA-DR+CD8+T细胞相比,CD38-HLA-DR+CD8+T细胞比例更能反映HIV/AIDS病人的免疫状态。
Objective To explore the potential relationship between CD38~+/~-HLA-DR~+CD8~+T cells and the immune status of HIV/AIDS patients,observe the percentage of two subsets and analyze the correlation with CD8+T cell count under different immune status.Methods PBMC samples from 46 HIV/AIDS patients were collected inDitan hospital,Beijing.The percentage of two activated subsets of CD38~+/~-HLA-DR~+CD8~+T cells were detectedby LSR Fortessa flow cytometry.We analyzed the percentage of CD38~+/~-HLA-DR~+CD8~+T cells and the correla-tion with CD8+T cell count,based on CD4+T cell count(CD4 count,CD4<200 cells/μl group and CD4>200 cells/μl group)and plasma viral load(VL,VL<105 copies/ml and VL>105 copies/ml)in patients' groups respec-tively.Results 1)In CD4 count group:higher percentage of CD38-HLA-DR+CD8+T cells was observed withCD4<200 cells/μl(P=0.02).There was no difference in CD38+HLA-DR+CD8+T cells percentage between thetwo groups(P >0.05).Only with CD4>200 cells/μl,CD38-HLA-DR+CD8+T cells percentage was positivelycorrelated with CD8 count(r>0.35,P<0.05).2)In VL group:there was no significant difference in the percent-age of CD38~+/~-HLA-DR~+CD8~+T cells between the two groups(P>0.05),and negative correlation with CD8 count(P>0.05).Conclusion CD8+T cells activation levels are increasing in HIV/AIDS patients.The percentage of CD38-HLA-DR+CD8+T cells could better reflect the immune status of HIV/AIDS patients.
Objective To explore the potential relationship between CD38~+/~-HLA-DR~+CD8~+T cells and the immune status of HIV/AIDS patients,observe the percentage of two subsets and analyze the correlation with CD8+T cell count under different immune status.Methods PBMC samples from 46 HIV/AIDS patients were collected inDitan hospital,Beijing.The percentage of two activated subsets of CD38~+/~-HLA-DR~+CD8~+T cells were detectedby LSR Fortessa flow cytometry.We analyzed the percentage of CD38~+/~-HLA-DR~+CD8~+T cells and the correla-tion with CD8+T cell count,based on CD4+T cell count(CD4 count,CD4<200 cells/μl group and CD4>200 cells/μl group)and plasma viral load(VL,VL<105 copies/ml and VL>105 copies/ml)in patients' groups respec-tively.Results 1)In CD4 count group:higher percentage of CD38-HLA-DR+CD8+T cells was observed withCD4<200 cells/μl(P=0.02).There was no difference in CD38+HLA-DR+CD8+T cells percentage between thetwo groups(P >0.05).Only with CD4>200 cells/μl,CD38-HLA-DR+CD8+T cells percentage was positivelycorrelated with CD8 count(r>0.35,P<0.05).2)In VL group:there was no significant difference in the percent-age of CD38~+/~-HLA-DR~+CD8~+T cells between the two groups(P>0.05),and negative correlation with CD8 count(P>0.05).Conclusion CD8+T cells activation levels are increasing in HIV/AIDS patients.The percentage of CD38-HLA-DR+CD8+T cells could better reflect the immune status of HIV/AIDS patients.
引文
[1]Trickey A,May MT,Schommers P,et al.CD4:CD8ratio and CD8+cell count for prognosticating mortality in HIV-infected patients on antiretroviral therapy,The Antiretroviral Therapy Cohort Collaboration(ART-CC)[J].Clinical Infectious Diseases,2017:959-966.(Epub ahead of print).
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[3]Hua S,Le′curoux C,Sa′ez-Cirio′n A,et al.Potential Role for HIV-Specific CD38-/HLA-DR+CD8+T Cells in Viral Suppression and Cytotoxicity in HIV Controllers[J].PLoS One,2014,9(7):e101920.
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[5]Doedens AL,Phan AT,Stradner MH,et al.Hypoxia-inducible factors enhance the effector responses of CD8+T cells to persistent antigen[J].Nat Immunol,2013,14(11):1173-1182.
[6]D'Ettorre G,Ceccarelli G,Serafino S,et al.Dominant enrichment of phenotypically activated CD38+HLA-DR+CD8+T cells,rather than CD38+HLA-DR+CD4+T cells,in HIV/HCV co-infected patients on antiretroviral therapy[J].Journal of Medical Virology,2016,88(8):1347-1356.
[7]郭伏平.长期抗逆转录病毒治疗的艾滋病患者免疫功能重建研究[D].北京:北京协和医学院、中国医学科学院、清华大学医学部,2013.
[8]Li N,Ji PY,Song LG,et al.The expression of molecule CD28and CD38on CD4(+)/CD8(+)T lymphocytes in thymus and spleen elicited by Schistosoma japonicum infection in mice model[J].Parasitology Research,2015,114(8):3047-3058.
[9]Manion M,Rodriguez B,Medvik K,et al.Interferon-alpha administration enhances CD8+T cell activation in HIV infection[J].PLoS One,2012(7):e30306.
[10]Hervas-Stubbs S,Riezu-Boj J-I,Gonzalez I,et al.Effects of IFN-a as a signal-3cytokine on human nave and antigenexperienced CD8(+)T cells[J].Eur J Immunol,2010,40(12):3389-3402.
[11]Imamichi H,Lempicki RA,Adelsberger JW,et al.The CD8+HLA-DR+T cells expanded in HIV-1infection are qualitatively identical to those from healthy controls[J].European Journal of Immunology,2012,42(10):2608-2620.
[12]Musyoki S,Mining S,Nyongesa P.Level of CD8TLymphocytes Activation in HIV-Infected Pregnant Women:In the Context of CD38and HLA-DR Activation Markers[J].Interdisciplinary Perspectives on Infectious Diseases,2014,2014(6):715279.
[13]Sachdeva M,Fischl MA,Pahwa R,et al.Immune Exhaustion Occurs Concomitantly With Immune Activation and Decrease in Regulatory T Cells in Viremic Chronically HIV-1-Infected Patients[J].JAIDS J Acquir Immune Defic Syndr,2010(54):447-454.
[14]Sa′ez-Cirio′n A,Lacabaratz C,Lambotte O,et al.HIV controllers exhibit potent CD8Tcell capacity to suppress HIV infection ex vivo and peculiar cytotoxic T lymphocyte activation phenotype[J].Proc Natl Acad Sci USA,2007(104):6776-6781.
[15]Sáezcirión A,Sinet M,Shin SY,et al.Heterogeneity in HIVsuppression by CD8 Tcells from HIV controllers:association with Gag-specific CD8Tcell responses[J].Journal of Immunology,2009,182(12):7828-7837.
[16]Deeks SG,Kitchen CMR,Liu L,et al.Immune activation set point during early HIV infection predicts subsequent CD4+T-cell changes independent of viral load[J].Blood,2004(104):942-947.
[17]Lederman MM,Funderburg NT,Sekaly RP,et al.Residual immune dysregulation syndrome in treated HIV infection[J].Advances in immunology,2013(119):51-83.
[18]Seu L,Sabbaj S,Duverger A,et al.Stable Phenotypic Changes of the Host T Cells Are Essential to the Long-Term Stability of Latent HIV-1Infection[J].Journal of Virology,2015,89(13):6656-6672.
[19]Wada NI,Jacobson LP,Margolick JB,et al.The effect of HAART-induced HIV suppression on circulating markers of inflammation and immune activation[J].AIDS,2015,29(4):463-471.
[2]D'Ettorre G,Ceccarelli G,Serafino S,et al.Dominant enrichment of phenotypically activated CD38+HLA-DR+CD8+T cells,rather than CD38+HLA-DR+CD4+T cells,in HIV/HCV co-infected patients on antiretroviral therapy[J].Journal of Medical Virology,2016,88(8):1347-1356.
[3]Hua S,Le′curoux C,Sa′ez-Cirio′n A,et al.Potential Role for HIV-Specific CD38-/HLA-DR+CD8+T Cells in Viral Suppression and Cytotoxicity in HIV Controllers[J].PLoS One,2014,9(7):e101920.
[4]Kahan SM,Wherry EJ,Zajac AJ.T cell exhaustion during persistent viral infections[J].Virology,2015,479-480(6):180-193.
[5]Doedens AL,Phan AT,Stradner MH,et al.Hypoxia-inducible factors enhance the effector responses of CD8+T cells to persistent antigen[J].Nat Immunol,2013,14(11):1173-1182.
[6]D'Ettorre G,Ceccarelli G,Serafino S,et al.Dominant enrichment of phenotypically activated CD38+HLA-DR+CD8+T cells,rather than CD38+HLA-DR+CD4+T cells,in HIV/HCV co-infected patients on antiretroviral therapy[J].Journal of Medical Virology,2016,88(8):1347-1356.
[7]郭伏平.长期抗逆转录病毒治疗的艾滋病患者免疫功能重建研究[D].北京:北京协和医学院、中国医学科学院、清华大学医学部,2013.
[8]Li N,Ji PY,Song LG,et al.The expression of molecule CD28and CD38on CD4(+)/CD8(+)T lymphocytes in thymus and spleen elicited by Schistosoma japonicum infection in mice model[J].Parasitology Research,2015,114(8):3047-3058.
[9]Manion M,Rodriguez B,Medvik K,et al.Interferon-alpha administration enhances CD8+T cell activation in HIV infection[J].PLoS One,2012(7):e30306.
[10]Hervas-Stubbs S,Riezu-Boj J-I,Gonzalez I,et al.Effects of IFN-a as a signal-3cytokine on human nave and antigenexperienced CD8(+)T cells[J].Eur J Immunol,2010,40(12):3389-3402.
[11]Imamichi H,Lempicki RA,Adelsberger JW,et al.The CD8+HLA-DR+T cells expanded in HIV-1infection are qualitatively identical to those from healthy controls[J].European Journal of Immunology,2012,42(10):2608-2620.
[12]Musyoki S,Mining S,Nyongesa P.Level of CD8TLymphocytes Activation in HIV-Infected Pregnant Women:In the Context of CD38and HLA-DR Activation Markers[J].Interdisciplinary Perspectives on Infectious Diseases,2014,2014(6):715279.
[13]Sachdeva M,Fischl MA,Pahwa R,et al.Immune Exhaustion Occurs Concomitantly With Immune Activation and Decrease in Regulatory T Cells in Viremic Chronically HIV-1-Infected Patients[J].JAIDS J Acquir Immune Defic Syndr,2010(54):447-454.
[14]Sa′ez-Cirio′n A,Lacabaratz C,Lambotte O,et al.HIV controllers exhibit potent CD8Tcell capacity to suppress HIV infection ex vivo and peculiar cytotoxic T lymphocyte activation phenotype[J].Proc Natl Acad Sci USA,2007(104):6776-6781.
[15]Sáezcirión A,Sinet M,Shin SY,et al.Heterogeneity in HIVsuppression by CD8 Tcells from HIV controllers:association with Gag-specific CD8Tcell responses[J].Journal of Immunology,2009,182(12):7828-7837.
[16]Deeks SG,Kitchen CMR,Liu L,et al.Immune activation set point during early HIV infection predicts subsequent CD4+T-cell changes independent of viral load[J].Blood,2004(104):942-947.
[17]Lederman MM,Funderburg NT,Sekaly RP,et al.Residual immune dysregulation syndrome in treated HIV infection[J].Advances in immunology,2013(119):51-83.
[18]Seu L,Sabbaj S,Duverger A,et al.Stable Phenotypic Changes of the Host T Cells Are Essential to the Long-Term Stability of Latent HIV-1Infection[J].Journal of Virology,2015,89(13):6656-6672.
[19]Wada NI,Jacobson LP,Margolick JB,et al.The effect of HAART-induced HIV suppression on circulating markers of inflammation and immune activation[J].AIDS,2015,29(4):463-471.
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