Kim Arthur Y, Lauer Georg M, Ouchi Kei, Addo Marylyn M, Lucas Michaela, Schulze Zur Wiesch Julian, Timm Joerg, Boczanowski Melinda, Duncan Jared E, Wurcel Alysse G, Casson Deborah, Chung Raymond T, Draenert Rika, Klenerman Paul, Walker Bruce D
Partners AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital, Harvard Medical School, 149 13th St 5th Fl, Boston, MA 02129, USA.
Blood. 2005 Feb 1;105(3):1170-8. doi: 10.1182/blood-2004-06-2336. Epub 2004 Sep 30.
CD8(+) T-cell responses are an essential antiviral host defense in persistent viral infections, and their sustained effectiveness is thought to be critically dependent on CD4(+) T-helper cells. To determine the relationship between HIV-1-induced CD4(+) T-cell depletion and hepatitis C virus (HCV)-specific CD8(+) T-cell responses during viral persistence, we studied 103 persons positive for HCV, 74 coinfected with HIV-1. CD8(+) T-cell responses to the entire HCV polyprotein were determined by using an interferon-gamma enzyme-linked immunospot (ELISpot) assay. Although HIV-1 infection by itself was not associated with a diminished HCV-specific response, HIV-1-associated CD4(+) depletion was associated with significantly lower HCV-specific CD8(+) T cells (R = 0.48, P < .0001). In contrast, declining CD4(+) counts over the same range were not associated with diminished Epstein-Barr virus (EBV)- (R = 0.19, P = .31) or HIV-1-specific (R = -0.13, P = .60) CD8(+) T-cell responses in persons infected with all viruses. These data indicate that frequencies of circulating HCV-specific CD8(+) T-cell responses are sensitive to absolute CD4(+) T-cell counts and provide a possible explanation for the accelerated HCV disease course in persons coinfected with HIV-1 and HCV.
CD8(+) T细胞应答是持续性病毒感染中至关重要的抗病毒宿主防御机制，其持续有效性被认为严重依赖于CD4(+)辅助性T细胞。为了确定病毒持续存在期间HIV-1诱导的CD4(+) T细胞耗竭与丙型肝炎病毒（HCV）特异性CD8(+) T细胞应答之间的关系，我们研究了103例HCV阳性患者，其中74例合并感染HIV-1。通过使用干扰素-γ酶联免疫斑点（ELISpot）测定法确定CD8(+) T细胞对整个HCV多聚蛋白的应答。虽然HIV-1感染本身与HCV特异性应答减弱无关，但HIV-1相关的CD4(+)细胞耗竭与HCV特异性CD8(+) T细胞显著减少相关（R = 0.48，P <.0001）。相比之下，在感染所有病毒的患者中，相同范围内CD4(+)计数的下降与EB病毒（EBV）特异性（R = 0.19，P =.31）或HIV-1特异性（R = -0.13，P =.60）CD8(+) T细胞应答减弱无关。这些数据表明，循环中HCV特异性CD8(+) T细胞应答的频率对绝对CD4(+) T细胞计数敏感，并为HIV-1和HCV合并感染患者中HCV疾病进程加速提供了一种可能的解释。
