Cellular Immunity to Hepatitis C Virus in HIV

描述：(申请人提供) 艾滋病毒和丙型肝炎病毒(丙型肝炎病毒)感染的流行在个人中相遇 非肠道暴露于血液，包括注射吸毒者和 血友病患者，混合感染率从60%到90%不等。 合并感染的患者进展为 终末期肝病，尽管艾滋病毒改变其病程的机制 人们对丙型肝炎病毒知之甚少。自相矛盾的是，艾滋病毒，一种免疫抑制剂 状态，导致肝病加速发展，而HAART是 也与肝功能衰竭有关。我们的中心假设是 外周和肝内丙型肝炎病毒特异的细胞免疫反应是 合并感染HIV的患者在质量和数量上的差异 与单一感染丙型肝炎病毒的人相比，这不仅仅是一种 免疫抑制程度的作用。我们的目标是确定 合并感染的人对丙型肝炎病毒的细胞免疫反应发生了变化， 确定免疫重建是否影响丙型肝炎病毒特异性细胞免疫，以及 如果对丙型肝炎病毒的细胞免疫反应与改善预后有关 抗丙型肝炎病毒治疗。为了解决这些假设，我们正在研究特定于丙型肝炎病毒的 三组人的细胞免疫反应：1)丙型肝炎病毒/艾滋病毒感染者与 单独的丙型肝炎病毒，2)在HAART之前和免疫期间感染艾滋病毒/丙型肝炎病毒的人 重建，以及3)艾滋病毒/丙型肝炎病毒携带者正在进入 干扰素-利巴韦林疗法。我们正在使用ELISPOTS来描述分泌物 干扰素-γ、肿瘤坏死因子α和白介素10 外周血单核细胞水平与肝脏浸润性 这些人群中的淋巴细胞。我们正在补充这些功能分析 用流式细胞术检测淋巴细胞的表型。 检测慢性丙型肝炎患者细胞免疫应答的变化 HIV可能有助于我们理解加速的 严重肝病的进展以及帮助确定人群的亚群 可能从丙型肝炎治疗中受益的艾滋病毒携带者。

DESCRIPTION: (Provided by Applicant) The epidemics of HIV and hepatitis C virus (HCV) infections meet in individuals with parenteral exposure to blood, including injecting drug users (IDU) and persons with hemophilia, where rates of coinfection range from 60-90 percent. Coinfected individuals have a significantly increased risk of progression to end-stage liver disease, though mechanisms by which HIV modifies the course of HCV are poorly understood. It is paradoxical that HIV, an immunosuppressive state, leads to an accelerated progression of liver disease, and that HAART is associated with liver failure as well. Our central hypothesis is that both peripheral and intrahepatic HCV-specific cellular immune responses are qualitatively and quantitatively different in patients coinfected with HIV compared with those with HCV monoinfection, and that this is not solely a function of the degree of immunosuppression. Our goals are to determine whether coinfected individuals have an altered cellular immune response to HCV, to determine if immune reconstitution impacts HCV-specific cellular immunity, and if cellular immune responses to HCV are associated with improved outcome with anti-HCV therapy. To address these hypotheses we are examining HCV-specific cellular immune responses in three groups: 1) individuals with HCV/HIV versus HCV alone, 2) individuals with HIV/HCV prior to HAART and during immune reconstitution, and 3) individuals with HIV/HCV who are entering a protocol of interferon-ribavirin therapy. We are using ELISPOTS to characterize secretion of interferon-gamma, tumor necrosis factor alfa, and interleukin-10 at the single cell level in peripheral mononuclear cells and liver-infiltrating lymphocytes in these populations. We are complementing these functional assays with flow cytometry to phenotypically characterize lymphocyte populations. Determining alterations in cellular immune responses to HCV in individuals with HIV may help us to understand the pathophysiology underlying the accelerated progression of severe liver disease as well as help define subgroups of persons with HIV who may benefit from treatment of hepatitis C.