慢性乙型肝炎患者外周血CD8~+CD28~+T淋巴细胞百分比的变化及其临床意义探讨
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摘要
目的探讨不同病程阶段的慢性乙型肝炎患者外周血CD8~+CD28~+T淋巴细胞百分比的变化,以及CD8~+CD28~+T淋巴细胞百分比变化与血清HBsAg水平的关系。方法 2018年4月～2018年8月我院诊治的慢性乙型肝炎患者88例,其中免疫耐受期20例,免疫清除期28例,非活动期20例,再活动期20例,另选择健康人20例。使用流式细胞术检测外周血CD8~+CD28~+T淋巴细胞百分比。结果健康人与免疫耐受期患者外周血CD8~+CD28~+T淋巴细胞百分比分别为(26.1±3.5)%和(26.3±3.4)%,差异无统计学意义(P>0.05);免疫清除期患者CD8~+CD28~+T淋巴细胞百分比为(40.1±4.7)%,显著高于健康人(P<0.05);非活动期和再活动期患者外周血CD8~+CD28~+T淋巴细胞百分比分别为(20.3±2.2)%和(26.1±2.2)%,显著低于健康人(P<0.05);外周血HBsAg低、中、高三组人群外周血CD8~+CD28~+T淋巴细胞百分比分别为(24.0±7.5)%、(28.4±8.9)%和(33.2±8.5)%,各组间差异有统计学意义(P<0.05)。结论不同病程阶段的慢性乙型肝炎患者外周血CD8~+CD28~+T淋巴细胞百分比存在明显差异,可能与病毒长期刺激机体免疫系统,导致免疫系统功能失调有关,而这种失调可能参与了慢性乙型肝炎的发病过程。
Objective To investigate the changes of peripheral blood CD8~+CD28~+T lymphocyte percentages in patients with hepatitis B. Methods A total of 88 patients with hepatitis B and 20 healthy individuals were recruited in 902 nd hospital of PLA between April 2018 and August 2018,and the patients with hepatitis B included patients in immune tolerance phase(n=20),immune clearance phase(n=28),low replication phase(n=20),and re-activation phase(n=20). The percentages of CD8~+CD28~+T lymphocytes in peripheral blood were measured by flow cytometry. Results The percentages of CD8~+CD28~+T lymphocytes in patients in immune tolerance phase were(26.3 ±3.4)%,not significantly different as compared to(26.1 ±3.5)% in healthy persons(P >0.05);the percentages of CD8~+CD28~+T lymphocytes in patients in immune clearance were(40.1 ±4.7)%,significantly higher than that in healthy control(P<0.05);the percentages of CD8~+CD28~+T lymphocytes in patients inactive phase and reactive stage were(20.3±2.2)% and(26.1±2.2)%,respectively,significantly lower than that in healthy control(P<0.05);the CD8~+CD28~+T lymphocytes in patients with high,moderate and low serum HBsAg level were(24.0 ±7.5)%,(28.4±8.9)% and(33.2±8.5)%,respectively,with statistically significant differences among them(P<0.05).Conclusions There are significant differences in the percentages of peripheral blood CD8~+CD28~+T lymphocytes in patients with hepatitis B at different immune phases,which might be related to the dysfunctions of immune system activated by the viral infection.
Objective To investigate the changes of peripheral blood CD8~+CD28~+T lymphocyte percentages in patients with hepatitis B. Methods A total of 88 patients with hepatitis B and 20 healthy individuals were recruited in 902 nd hospital of PLA between April 2018 and August 2018,and the patients with hepatitis B included patients in immune tolerance phase(n=20),immune clearance phase(n=28),low replication phase(n=20),and re-activation phase(n=20). The percentages of CD8~+CD28~+T lymphocytes in peripheral blood were measured by flow cytometry. Results The percentages of CD8~+CD28~+T lymphocytes in patients in immune tolerance phase were(26.3 ±3.4)%,not significantly different as compared to(26.1 ±3.5)% in healthy persons(P >0.05);the percentages of CD8~+CD28~+T lymphocytes in patients in immune clearance were(40.1 ±4.7)%,significantly higher than that in healthy control(P<0.05);the percentages of CD8~+CD28~+T lymphocytes in patients inactive phase and reactive stage were(20.3±2.2)% and(26.1±2.2)%,respectively,significantly lower than that in healthy control(P<0.05);the CD8~+CD28~+T lymphocytes in patients with high,moderate and low serum HBsAg level were(24.0 ±7.5)%,(28.4±8.9)% and(33.2±8.5)%,respectively,with statistically significant differences among them(P<0.05).Conclusions There are significant differences in the percentages of peripheral blood CD8~+CD28~+T lymphocytes in patients with hepatitis B at different immune phases,which might be related to the dysfunctions of immune system activated by the viral infection.
引文
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[12] Jenkins MK,Ashwell JD,Schwartz RH. Allogeneic non-T spleencells restore the responsiveness of normal T cell clones stim-ulated with antigen and chemically modified antigen-presentingcells. J Immunol,1988,140(10):3324-3330.
[13] Mueller DL,Jenkins MK,Schwartz RH. An accessory cell-de-rived costimulatory signal acts independently of protein kinaseC activation to allow T cell proliferation and prevent the in-duction of unresponsiveness. J Immunol,1989,142(8):2617-2628.
[14] Bruss V. Envelopment of the hepatitis B virus nucleocapsid.Virus Res,2004,106(2):199-209.
[15] Uzun L,Say R,Unal S,et al. Hepatitis B surface antibodypurification with hepatitis B surface antibody imprinted poly(hydroxyethyl methacrylate-N-methacryloyl-L-tyrosine methylester)particles. J Chromatogr Analyt Biomed Lif Sci,2009,877(3):181-188.
[16] Assrir N,Soussan P,Kremsdorf D,et al. Role of the hepatitis Bvirus proteins in pro-and anti-apoptotic processes. FrontBiosci(Landmark Ed),2010,15:12-24.
[17] Liaw YF. Natural history of chronic hepatitis B virus infectionand long-term outcome under treatment. Liver Int,2009,29(S1):100-107.
[18] Lenschow DJ,Zeng Y,Thistlethwaite JR,et al. Long-term sur-vival of xenogeneic pancreatic islet grafts induced by CT-LA4lg. Science,1992,257(5071):789-792.
[19] Zhang S,Guo H,Smith R. Dynamical analysis for a hepatitis Btransmission model with immigration and infection age. MathBiosci Eng,2018,15(6):1291-1313.
[20] Pandey A,Ezemenari S,Liaukovich M,et al. A Rare Case ofPembrolizumab-Induced Reactivation of Hepatitis B. Case RepOncol Med,2018,2018:5985131.
[21] Katoonizadeh A,Motamed-Gorji N,Sharafkhah M,et al. Intra-fa-milial Transmission of Chronic Hepatitis B Infection:A LargePopulation-Based Cohort Study in Northern Iran. Arch IranMed,2018,21(10):436-442.
[2] Chen P,Yu C,Ruan B,et al. Prevalence of hepatitis B ininsular regions of southeast China:a community-based study.PLoS One,2013,8(2):e56444.
[3] Hong MZ,Huang WQ,Min F,et al. Enhanced HBs Ag synthesiscorrelates with increased severity of fibrosis in chronichepatitis B patients. PLo S One,2014,9(1):e87344.
[4] Bertoletti A,Maini M,Williams R. Role of hepatitis B virusspecific cytotoxic T cells in liver damage and viral control.Antiviral Res,2003,60(2):61-66.
[5]秦浩歌,颜迎春,吴晓枫,等.慢性乙型肝炎患者和无症状病毒携带者外周血B淋巴细胞亚群的变化.中华肝脏病杂志,2006,14(10):773-774.
[6]张建春,翁锡定,陈孙云,等.乙型肝炎患者外周血T淋巴细胞亚群的变化.实用肝脏病杂志,2013,15(4):356-357.
[7] Evans EJ,Esnouf RM,Manso-Sancho R,et al. Crystal structureof a soluble CD28-Fab complex. Nat Immunol,2005,6(3):271-279.
[8] Liang Y,Cucchetti M,Roncagalli R,et al. The lymphoid lin-eage-specific actin-uncapping protein Rltpr is essential for cos-timulation via CD28 and the development of regulatory Tcells. Nat Immunol,2013,14(8):858-866.
[9]张泉,邱思芳,赵逵,等.结直肠癌及腺瘤患者CD4~+、CD8~+和CD28~+T淋巴细胞的亚群变化及临床意义.中国癌症杂志,2018,28(8):577-583.
[10] Ndlovu H,Darby M,Froelich M,et al. Inducible deletion ofCD28 prior to secondary nippostrongylus brasiliensis infectionimpairs worm expulsion and recall of protective memoryCD4(~+)T cell responses. PLo S Pathog,2014,10(2):e1003906.
[11]中华医学会肝病学分会和感染病学分会.慢性乙型肝炎防治指南(2015年版).实用肝脏病杂志,2016,19(3):Ⅴ-ⅩⅩⅢ.
[12] Jenkins MK,Ashwell JD,Schwartz RH. Allogeneic non-T spleencells restore the responsiveness of normal T cell clones stim-ulated with antigen and chemically modified antigen-presentingcells. J Immunol,1988,140(10):3324-3330.
[13] Mueller DL,Jenkins MK,Schwartz RH. An accessory cell-de-rived costimulatory signal acts independently of protein kinaseC activation to allow T cell proliferation and prevent the in-duction of unresponsiveness. J Immunol,1989,142(8):2617-2628.
[14] Bruss V. Envelopment of the hepatitis B virus nucleocapsid.Virus Res,2004,106(2):199-209.
[15] Uzun L,Say R,Unal S,et al. Hepatitis B surface antibodypurification with hepatitis B surface antibody imprinted poly(hydroxyethyl methacrylate-N-methacryloyl-L-tyrosine methylester)particles. J Chromatogr Analyt Biomed Lif Sci,2009,877(3):181-188.
[16] Assrir N,Soussan P,Kremsdorf D,et al. Role of the hepatitis Bvirus proteins in pro-and anti-apoptotic processes. FrontBiosci(Landmark Ed),2010,15:12-24.
[17] Liaw YF. Natural history of chronic hepatitis B virus infectionand long-term outcome under treatment. Liver Int,2009,29(S1):100-107.
[18] Lenschow DJ,Zeng Y,Thistlethwaite JR,et al. Long-term sur-vival of xenogeneic pancreatic islet grafts induced by CT-LA4lg. Science,1992,257(5071):789-792.
[19] Zhang S,Guo H,Smith R. Dynamical analysis for a hepatitis Btransmission model with immigration and infection age. MathBiosci Eng,2018,15(6):1291-1313.
[20] Pandey A,Ezemenari S,Liaukovich M,et al. A Rare Case ofPembrolizumab-Induced Reactivation of Hepatitis B. Case RepOncol Med,2018,2018:5985131.
[21] Katoonizadeh A,Motamed-Gorji N,Sharafkhah M,et al. Intra-fa-milial Transmission of Chronic Hepatitis B Infection:A LargePopulation-Based Cohort Study in Northern Iran. Arch IranMed,2018,21(10):436-442.
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