慢性乙型肝炎患者外周血CD8^+T淋巴细胞功能的变化

Changes of CD8^+T cell function in patients with chronic hepatitis B

目的探讨慢性乙型肝炎患者CD8+T淋巴细胞功能的变化。方法利用主要组织相容性复合物(MHC)-抗原肽四聚体标记技术检测HBV的特异性CD8+T淋巴细胞,并检测其细胞因子的分泌能力,分析其与病毒学指标及临床生化指标的关系。结果人类白细胞相关抗原(HLA)-A基因型为A02或A24的42例患者中,有11例患者至少检出一种被四聚体识别的HBV特异性CD8+T淋巴细胞,白细胞介素2(IL-2)及γ(IFN-γ)干扰素的分泌能力相对于其自身的外周血总CD8+T淋巴细胞显著降低(t=14.231、10.450,P<0.01)。检出抗原特异性CD8+T淋巴细胞的患者,其血清ALT的水平较阴性患者高(t=2.306,P<0.05),而HBV DNA水平却相对低(t=-4.447,P<0.001)。结论慢性乙型肝炎患者外周血的抗原特异性CD8+T淋巴细胞的功能存在明显的缺陷,可能与病毒抗原的持续刺激导致功能耗竭有关。

Objective To explore the changes of CD8 ＋ T cells function in patients with chronic hepatitis B （CHB）. Methods The HBV-specific CD8 ＋ T cells from patients with CHB were detected by staining of major histocompatibility complex （MHC）-peptide tetramers.Cytokine secretion ability of HBV-specific CD8 ＋ T cells was measured to analyze,the relationship of HBV-specific CD8 ＋ T cells with clinical biochemical and virology index.Results Among 42 patients with human leukocyte antigen （HLA）-A02 or A24 genotype,9 of them had HBV-specific CD8 ＋ T cells,which were detected by tetramers from peripheral blood.The HBV-specific CD8 ＋ T cells expressed significantly lower interleukin2 （IL-2 ）and interferon gamma（IFN-γ）than their counterpart CD8 ＋ T cells.In addition,patients with HBV-specific CD8 ＋ T cells had higher level of alanine aminotransferase （ALT）and lower HBV DNA load than those without HBV-specific CD8 ＋ T cells. Conclusion Persistent stimulation of HBV antigen is one of the causes of HBV-specific CD8 ＋ T cell dysfunction in patients with CHB.Detection of HBV-specific CD8 ＋ T cells from peripheral blood suggests an excessive anti-virus immune response in CHB patients.