慢性乙型肝炎患者外周血抗原特异性CD8~+T细胞功能的初步分析

目的评价慢性乙型肝炎(CHB)患者外周血抗原特异性CD8+T细胞的功能及与临床相关指标的关系。方法采用主要组织相容性复合物(MHC)-抗原肽四聚体标记技术检测CHB患者外周血乙型肝炎病毒(HBV)抗原特异性CD8+T细胞,并对其细胞因子分泌能力进行检测,分析其与临床生化和病毒学指标的关系。结果 35例人类白细胞相关抗原(HLA)-A基因型为A02或A24的患者中有9例患者至少检出1种被四聚体识别的HBV抗原特异性CD8+T细胞,其白细胞介素2(IL-2)和γ干扰素(IFN-γ)的分泌能力明显低于其自身的外周血总CD8+T细胞。检出抗原特异性CD8+T细胞患者的血清丙氨酸氨基转移酶(ALT)水平明显高于阴性患者,而HBV DNA水平低于阴性患者。结论 CHB患者外周血抗原特异性CD8+T细胞存在明显的功能缺陷,可能因病毒抗原持续刺激造成功能耗竭,但外周血出现抗原特异性CD8+T细胞仍表明患者体内出现较强抗病毒免疫反应。

Primary analysis on the function of peripheral blood HBV-specific CD8^＋ T cells from patients with chronic hepatitis B

Objective To evaluate the function of peripheral blood hepatitis B virus （HBV）-specific CD8 ^＋ T cells from patients with chronic hepatitis B（CHB） , and assess its relationship with clinical relative parameters. Methods The HBV-specific CD8^ ＋ T cells were detected by staining of major histocompatibility complex （MHC） -peptide tetramers in patients with CHB. The HBV-specifie CD8 ^＋ T cells were analyzed for cytokine secretion ability. The relationship of HBV-specifie CD8^＋ T cells with clinical biochemical and viral indices was analyzed. Results A total of 9 of 35 patients with human leukocyte antigen （HLA）-A02 genotype or A24 genotype had HBV-speeific CD8 ^＋ T ceils recognized by tetramers in peripheral blood. The HBV-specifie CD8^ ＋ T cells expressed significantly lower interleukin 2 （IL-2） and interferon gamma （IFN-γ） than their counterpart CD8 ^＋ T cells. The patients who can be found HBV- specific CD8 ^＋ T cells had higher level of alanine aminotransferase（ALT） and lower HBV DNA load than those without HBV-specifie CD8 ^＋ T cells. Conclusions Persistent stimulation of HBV antigen is one of the causes of HBV-specific CD8^＋ T cell dysfunction in patients with CHB. The patients who can be found HBV-specifie CD8^＋ T cells in peripheral blood could have strong anti-virus immunity.