Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain.
J Acquir Immune Defic Syndr. 2011 May 1;57(1):1-8. doi: 10.1097/qai.0b013e31821024e7.
Cellular responses against hepatitis C virus (HCV) are impaired in HIV/HCV-coinfected patients showing uncontrolled viral replication and immune suppression. Very few studies have explored to what extent HCV-specific response improves as a consequence of control of HIV replication by highly active antiretroviral therapy. We compared HCV-specific T-cell responses between HIV/HCV-coinfected patients, showing complete viral suppression, and HCV-monoinfected patients.
HCV-specific T-cell responses were examined in 50 interferon-naive patients with chronic hepatitis C: 27 HCV-mono-infected and 23 HIV/HCV-coinfected on highly active antiretroviral therapy and undetectable HIV load. Production of interferon-γ and tumor necrosis factor-α was simultaneously measured in response to genotype-matched overlapping peptides spanning the whole HCV proteome by flow cytometry. Differences between groups were tested using nonparametric tests.
More than half of patients presented CD4+ (60%) or CD8+ (57%) response to at least one HCV protein with no significant differences between both groups. Intensity and breadth of response were also similar between groups. The functional profile of response was represented, in both groups, mainly by monofunctional subsets, although there were some differences between CD4+ and CD8+ T-cell response. CD8+ response was mediated almost exclusively by monofunctional interferon-γ+ cells, whereas bifunctional interferon-γ+ tumor necrosis factor-α+ cells showed a moderate contribution to CD4+ response. Most of the CD8+ response was mediated by interferon-γ, whereas tumor necrosis factor-α was the highest contributor to CD4+ response.
Our study demonstrates that in HIV/HCV-coinfected patients with maximal HIV suppression under highly active antiretroviral therapy, several characteristics of anti-HCV T-cell response are similar to those found in HCV-monoinfected patients, suggesting that control of HIV replication might improve HCV-specific T-cell response in HIV/HCV-coinfected patients.
在 HIV/HCV 合并感染的患者中，由于病毒复制失控和免疫抑制，细胞对丙型肝炎病毒 (HCV) 的反应受损。很少有研究探讨在高效抗逆转录病毒疗法控制 HIV 复制的情况下，HCV 特异性反应在多大程度上得到改善。我们比较了 HIV/HCV 合并感染的患者（表现出完全病毒抑制）和 HCV 单感染患者之间的 HCV 特异性 T 细胞反应。
对 50 名干扰素初治慢性丙型肝炎患者进行 HCV 特异性 T 细胞反应检测：27 名 HCV 单感染和 23 名接受高效抗逆转录病毒治疗且 HIV 载量不可检测的 HIV/HCV 合并感染患者。通过流式细胞术同时检测对基因型匹配的涵盖整个 HCV 蛋白质组的重叠肽产生的干扰素-γ和肿瘤坏死因子-α。使用非参数检验测试组间差异。
超过一半的患者对至少一种 HCV 蛋白有 CD4+（60%）或 CD8+（57%）的反应，两组之间无显著差异。两组之间的反应强度和广度也相似。两组的反应功能谱均主要由单功能亚群代表，尽管 CD4+和 CD8+T 细胞反应之间存在一些差异。CD8+反应几乎完全由单功能干扰素-γ+细胞介导，而干扰素-γ+肿瘤坏死因子-α+双功能细胞对 CD4+反应有适度贡献。大多数 CD8+反应由干扰素-γ介导，而肿瘤坏死因子-α是 CD4+反应的最高贡献者。
我们的研究表明，在接受高效抗逆转录病毒疗法治疗且 HIV 得到最大抑制的 HIV/HCV 合并感染患者中，几种抗 HCV T 细胞反应的特征与 HCV 单感染患者相似，这表明控制 HIV 复制可能改善 HIV/HCV 合并感染患者的 HCV 特异性 T 细胞反应。
