中华实验和临床感染病杂志（电子版）
中華實驗和臨床感染病雜誌（電子版）
중화실험화림상감염병잡지（전자판）
CHINESE JOURNAL OF EXPERIMENTAL AND CLINICAL INFECTIOUS DISEASES(ELECTRONIC VERSION)
2013年
5期
665-669
,共5页
陈旭丹%刘琼%李新华%谢冬英
陳旭丹%劉瓊%李新華%謝鼕英
진욱단%류경%리신화%사동영
肝炎病毒,乙型%HBV特异性CD8+T细胞%免疫球蛋白粘蛋白分子-3%程序性死亡受体-1分子%γ-干扰素
肝炎病毒,乙型%HBV特異性CD8+T細胞%免疫毬蛋白粘蛋白分子-3%程序性死亡受體-1分子%γ-榦擾素
간염병독,을형%HBV특이성CD8+T세포%면역구단백점단백분자-3%정서성사망수체-1분자%γ-간우소
Hepatitis B virus%HBV specific CD8+ T cells%Tim-3%PD-1%IFN-γ
目的：研究免疫球蛋白黏蛋白分子-3（Tim-3）和程序性死亡受体-1分子（PD-1）在慢性乙型肝炎病毒（HBV）感染患者外周血HBV特异性CD8+ T细胞表面的表达模式，了解其与γ-干扰素（IFN-γ）产生的关系，并探讨其临床意义。方法采用流式细胞术检测主要组织相容性复合体-2（HLA-A2）阳性的78例临床类型不同的慢性HBV感染患者HBV特异性CD8+ T细胞表面分子Tim-3和PD-1的表达，ELISA方法检测外周血单个核细胞（PBMC）培养上清液中IFN-γ的水平。结果慢性HBV感染者Tim-3+/PD-1+HBV特异性CD8+ T细胞比例占总的HBV特异性CD8+ T细胞的58%，Tim-3-/PD-1+细胞比例为24%，Tim-3-/PD-1-比例16%，Tim-3+/PD-1-比例最低为2%。临床病情越严重的临床类型中，Tim-3+/PD-1+HBV特异性CD8+ T细胞比例越高，慢性乙型肝炎轻中度组为（52.05±18.68）%，重度肝炎组为（59.66±19.25）%，重型肝炎组最高为（68.72±17.21）%；各组与非活动性携带者组比较，P值分别为0.007、0.009、0.000。重型组与轻中度组比较，P =0.018。Tim-3+/PD-1+在HBV特异性CD8+ T细胞的表达与细胞培养上清液IFN-γ的水平呈负相关性（r =-0.466，P ＜0.001）。结论在HBV特异性CD8+ T细胞中，Tim-3和PD-1共同表达是其主要表达模式，Tim-3和PD-1的高表达可能负性调控IFN-γ的产生，从而影响慢性HBV感染的疾病进展和结局。
目的：研究免疫毬蛋白黏蛋白分子-3（Tim-3）和程序性死亡受體-1分子（PD-1）在慢性乙型肝炎病毒（HBV）感染患者外週血HBV特異性CD8+ T細胞錶麵的錶達模式，瞭解其與γ-榦擾素（IFN-γ）產生的關繫，併探討其臨床意義。方法採用流式細胞術檢測主要組織相容性複閤體-2（HLA-A2）暘性的78例臨床類型不同的慢性HBV感染患者HBV特異性CD8+ T細胞錶麵分子Tim-3和PD-1的錶達，ELISA方法檢測外週血單箇覈細胞（PBMC）培養上清液中IFN-γ的水平。結果慢性HBV感染者Tim-3+/PD-1+HBV特異性CD8+ T細胞比例佔總的HBV特異性CD8+ T細胞的58%，Tim-3-/PD-1+細胞比例為24%，Tim-3-/PD-1-比例16%，Tim-3+/PD-1-比例最低為2%。臨床病情越嚴重的臨床類型中，Tim-3+/PD-1+HBV特異性CD8+ T細胞比例越高，慢性乙型肝炎輕中度組為（52.05±18.68）%，重度肝炎組為（59.66±19.25）%，重型肝炎組最高為（68.72±17.21）%；各組與非活動性攜帶者組比較，P值分彆為0.007、0.009、0.000。重型組與輕中度組比較，P =0.018。Tim-3+/PD-1+在HBV特異性CD8+ T細胞的錶達與細胞培養上清液IFN-γ的水平呈負相關性（r =-0.466，P ＜0.001）。結論在HBV特異性CD8+ T細胞中，Tim-3和PD-1共同錶達是其主要錶達模式，Tim-3和PD-1的高錶達可能負性調控IFN-γ的產生，從而影響慢性HBV感染的疾病進展和結跼。
목적：연구면역구단백점단백분자-3（Tim-3）화정서성사망수체-1분자（PD-1）재만성을형간염병독（HBV）감염환자외주혈HBV특이성CD8+ T세포표면적표체모식，료해기여γ-간우소（IFN-γ）산생적관계，병탐토기림상의의。방법채용류식세포술검측주요조직상용성복합체-2（HLA-A2）양성적78례림상류형불동적만성HBV감염환자HBV특이성CD8+ T세포표면분자Tim-3화PD-1적표체，ELISA방법검측외주혈단개핵세포（PBMC）배양상청액중IFN-γ적수평。결과만성HBV감염자Tim-3+/PD-1+HBV특이성CD8+ T세포비례점총적HBV특이성CD8+ T세포적58%，Tim-3-/PD-1+세포비례위24%，Tim-3-/PD-1-비례16%，Tim-3+/PD-1-비례최저위2%。림상병정월엄중적림상류형중，Tim-3+/PD-1+HBV특이성CD8+ T세포비례월고，만성을형간염경중도조위（52.05±18.68）%，중도간염조위（59.66±19.25）%，중형간염조최고위（68.72±17.21）%；각조여비활동성휴대자조비교，P치분별위0.007、0.009、0.000。중형조여경중도조비교，P =0.018。Tim-3+/PD-1+재HBV특이성CD8+ T세포적표체여세포배양상청액IFN-γ적수평정부상관성（r =-0.466，P ＜0.001）。결론재HBV특이성CD8+ T세포중，Tim-3화PD-1공동표체시기주요표체모식，Tim-3화PD-1적고표체가능부성조공IFN-γ적산생，종이영향만성HBV감염적질병진전화결국。
Objective To study the patterns of expression of T-cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) and programmed death1 (PD-1) on HBV specific CD8+ T cells in chronic hepatitis B virus infection patients (CHB) . Ivestigate the correlation between Tim-3 and PD-1 and production of interferon gamma (IFN-γ) and its clinical meanings. Methods The expression of Tim-3 and PD-1 on HBV specific CD8+ T cells in 78 major histocompatibility complex-2 (HLA-A2) positive HBV patients with different clinical types were detected by flow cytometry. The level of IFN-γ in the supernatant of culture of peripheral blood mononuclear cell (PBMC) were detected by double antibody sandwich ELISA. Results In chronic HBV infection patients, 58% of HBV-specific CD8+ T cells are Tim-3+/PD-1+ cells, 24%are Tim-3-/PD-1+ cells. The ratio of Tim-3-/PD-1- cells was 16% and the Tim-3+/PD-1- cells are the lowest with 2%. The proportion of Tim-3+/PD-1+ HBV-specific CD8+ T cells increased consistent with the clinical severity. The ratio of Tim-3+/PD-1+ HBV-specific CD8+ T cells is (33.93 ± 10.80)% in the inactive HBsAg carriers. The ratio of Tim-3+/PD-1+ cells in mild and moderate chronic hepatitis patients are (52.05 ± 18.68)%, (59.66 ± 19.25)% are Tim-3+/PD-1+ cells in severe hepatitis, and (68.72 ± 17.21)% are Tim-3+/PD-1+ cells in hepatic failure, which is the highest. Compared with inactive HBsAg carriers, P = 0.007, 0.009, 0.000. Compare hepatic failure and mild and moderate chronic hepatitis, P = 0.018. The percentage of Tim-3+/PD-1+ HBV-specific CD8+ T cells negatively correlate with the level of IFN-γ in culture supernatant. Conclusions sCo-expression of Tim-3 and PD-1 on HBV-specific CD8+ T cells is the main pattern in HBV patients. High expression of Tim-3 and PD-1 may negatively control the production of IFN-γ, which may influence the outcomes and disease progression in chronic HBV infection.
