Medical Research Council, Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
Eur J Immunol. 2010 Apr;40(4):1036-41. doi: 10.1002/eji.200939634.
HIV-specific CTL play an important role in the host control of HIV infection. HIV-nef may facilitate escape of HIV-infected cells from CTL recognition by selectively downregulating the expression of HLA-A and HLA-B molecules, while surface expression of HLA-C is unaffected. The HLA-C-restricted CTL responses have previously been largely ignored and poorly characterized. We examined the frequency, function, and phenotype of HLA-C-restricted CTL in ten antiretroviral therapy-naïve Caucasian and African individuals with chronic HIV-1 infection (for at least 8 years; CD4 cell counts in the range of 50-350) who carried the HLA-Cw04 allele. HLA-Cw04-restricted CTL that recognize a conserved epitope within HIV-1 envelope (aa 375-383 SF9) were analyzed using IFN-gamma ELISPOT assays and phenotypic analysis was carried out by flow cytometry. HLA-C-restricted CTL play an important role in the HIV-specific response, and can account for as much as 54% of the total response. HLA-C-restricted CTL are functionally and phenotypically identical to HLA-A- and HLA-B-restricted CTL. HLA-C-restricted CTL in chronic HIV infection are memory cells of an intermediate phenotype, characterized by high CD27 and low CD28 expression and lack of perforin production.
HIV 特异性 CTL 在宿主控制 HIV 感染中发挥重要作用。HIV-nef 可能通过选择性地下调 HLA-A 和 HLA-B 分子的表达来促进 HIV 感染细胞逃避 CTL 的识别，而 HLA-C 的表面表达不受影响。以前，HLA-C 限制性 CTL 反应很大程度上被忽视和描述不足。我们研究了 10 名未经抗逆转录病毒治疗的白人（至少感染 HIV-1 8 年；CD4 细胞计数在 50-350 之间）和 10 名非洲人慢性 HIV-1 感染者中 HLA-Cw04 等位基因的频率、功能和表型。使用 IFN-γ ELISPOT 测定分析识别 HIV-1 包膜内保守表位（aa375-383SF9）的 HLA-Cw04 限制性 CTL，并通过流式细胞术进行表型分析。HLA-C 限制性 CTL 在 HIV 特异性反应中发挥重要作用，其比例高达 54%。HLA-C 限制性 CTL 在功能和表型上与 HLA-A 和 HLA-B 限制性 CTL 相同。慢性 HIV 感染中的 HLA-C 限制性 CTL 是中间表型的记忆细胞，其特征是 CD27 高表达和 CD28 低表达，缺乏穿孔素的产生。
