Cellular Immunity to Hepatitis C Virus in HIV

描述：（申请人提供） HIV和丙型肝炎病毒（HCV）感染的流行在个体中相遇 肠胃外接触血液，包括注射毒品使用者（IDU）， 血友病患者，其中合并感染率为60- 90%。 合并感染的个体进展至 终末期肝病，虽然艾滋病毒改变的机制， 对HCV了解甚少。这是矛盾的，艾滋病毒，一种免疫抑制剂， 所述，导致肝脏疾病的加速进展，并且HAART是 也会导致肝功能衰竭我们的核心假设是， 外周和肝内HCV特异性细胞免疫应答是 在合并感染HIV的患者中， 与HCV单一感染者相比，这不仅仅是一个 免疫抑制程度的函数。我们的目标是确定 合并感染的个体对HCV的细胞免疫应答改变， 确定免疫重建是否影响HCV特异性细胞免疫，以及 如果对HCV的细胞免疫应答与改善的结果相关， 抗HCV治疗。为了解决这些假设，我们正在研究HCV特异性 细胞免疫反应在三组：1）个人与HCV/HIV与 单独HCV，2）HAART前和免疫治疗期间感染HIV/HCV的个体 重建，和3）与艾滋病毒/丙型肝炎病毒的个人谁是进入一个协议， 干扰素-利巴韦林治疗。我们使用ELISPOTS来表征分泌 干扰素-γ、肿瘤坏死因子α和白细胞介素-10的水平 外周血单个核细胞中的单个细胞水平和肝脏浸润 这些人群中的淋巴细胞。我们正在补充这些功能检测 用流式细胞术来表征淋巴细胞群的表型。 确定HCV感染者对HCV细胞免疫应答的改变 艾滋病毒可能有助于我们了解加速艾滋病毒感染的病理生理学基础。 严重肝病的进展以及帮助定义人群亚组 感染HIV的人可能会从丙型肝炎的治疗中受益。

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.