乙型肝炎患者HBcAg特异性细胞毒性T细胞的检测及其与临床疾病状态的关系

Detection of HBcAg-specific cytotoxic lymphocytes and their association with clinical status in patients with hepatitis B

目的通过定量分析HLAA2402限制性的乙型肝炎病毒(HBV)特异性的细胞毒性T细胞(CTL)来研究急性自限性和慢性持续性乙型肝炎患者体内免疫反应的差异。方法从急性和慢性乙型肝炎感染患者外周血中提取外周血单个核淋巴细胞(PBMC),用HLAA2402HBV肽链四聚体复合体染色后,用流式细胞仪检测HBV特异性CTL细胞。同时使用酶联免疫斑点法来检测部分患者的CTL细胞分泌干扰素(IFN)γ的水平。结果在7例急性乙型肝炎的急性期,可以检测到高水平的HBV特异性的CTL细胞,而在急性乙型肝炎的恢复期,HBcAg特异性CTL细胞的水平可以明显下降。在13例慢性乙型肝炎患者中,除了1例慢性肝炎急性暴发患者之外,均不能检测到HBcAg特异性CTL细胞。IFNγ的分泌与这些结果相一致。结论HBcAg特异性CTL细胞在急性肝炎患者清除乙型肝炎病毒的过程中可能起到至关重要的作用。

Objective To investigate the difference of host immune response specific to hepatitis B virus(HBV)infections between acute self limited and chronic persistent hepatitis by quantitative analysis of HLA A*2402 restricted HBcAg specific cytotoxic T lymphocyte cells (CTL) cells. Methods The frequency of HBV specific CTL cells in the peripheral blood mononuclear cells(PBMCs) from 20 patients infected with HBV were quantified by ELISPOT assays and flow cytometry using one HLA A*2402 HBV, 7 with acute HB and 13 with chronic HB, peptide tetrameric complex. Results High frequencies of circulating HBcAg specific CTL cells were detected in most individuals with acute HBV infection while the number of these cells was significantly reduced at the convalenscent stage. HBcAg specific CTL cells were not detected in the PBMC from individuals with chronic HBV infection except for one patient with an acute infection exacerbation. Conclusion HBcAg specific CTL cells may play a crucial role in complete clearance of HBV from patients with acute HBV hepatitis.