解放军医学杂志2011,Vol.36Issue(4):361-364,4.
乙肝患者HBV特异性细胞毒T淋巴细胞的分析
Analysis of HBV-specific cytotoxic T lymphocytes in patients with hepatitis B
摘要
Abstract
Objective To investigate the expression feature of hepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTL),and analyze the role of CTL in immune response. Methods Peripheral venous blood was collected from 40 acute hepatitis B (AHB)patients hospitalized from Oct. 2008 to Jun. 2010 in 302 Hospital of PLA for the detection of human leucocyte antigen-A2 (HLA-A2).Out of the 40 patients, lS were HLA-A2-positive, and their peripheral blood mononuclear cells were isolated at acute phase and convalescent phase if the patients could be contacted. Six HLA-A2-negative AHB patients, 18 HLA-A2-positive chronic HB patients and 6 HLA-A2-positive normal persons served as controls. The CTL was stained by fluorescence-labeled ant1-CD3 monoclonal antibody, anti-CDS monoclonal antibody and HBV epitopic pentamers (S183-191, S335-343), and examined with flow cytometry, then analyzed by software Cell-quest. The peak value of alanine aminotransferase (ALT) and HBV load was detected at acute phase of patients, and the correlation was analyzed. Results The average frequencies were 0.23% ± 0.18% for HBsAgl83-l91-specific CTL and 0.49 %±0.31%for HBsAg335-343-specific CTL at the acute phase of the 18 AHB patients, and they were significantly higher than those in patients with chronic HB, in whom CTL frequencies were 0.07% ± 0.03% for HBsAgl83-l91-specific CTL and 0.08%±0.04% for HBsAg335-343-specific CTL ( P<0.01) . There was no correlation between the frequency of HBsAgl83-l91-specific CTL and the peak value of ALT ( r=0.4506, P=0.0528), while the frequency of HBsAg335-343-specific CTL was correlated with ALT level ( r=0.5642, P=0.0119).Neither the two CTL frequencies showed correlation with virus load. Compared with the acute phase, the CTL frequencies obviously decreased at convalescent phase ( P=0.011) . Both kinds of CTL were not detectable in HLA-A2-negative AHB patients and HLA-A2-positive healthy individuals. Conclusion HBV-specific CTL may play an important role in both virus clearance and liver impairment. CTL targeting to different HBV epitopes may contribute to the difference.关键词
肝炎病毒,乙型/HLA抗原/T淋巴细胞,细胞毒性分类
医药卫生引用本文复制引用
丁宁,黄丽利,刘妍,范振平,刘立明,赵平,靳雪源,叶海燕,徐东平..乙肝患者HBV特异性细胞毒T淋巴细胞的分析[J].解放军医学杂志,2011,36(4):361-364,4.基金项目
国家自然科学基金(30771898) (30771898)
军队"十一五"医药卫生科研杰出人才项目(06J024) (06J024)
国家科技重大专项课题(2009ZX10005-017) (2009ZX10005-017)