Immune responses to acute HIV infection

在急性HIV感染期间由高病毒复制引起的免疫应答和致病事件决定了晚期感染中的HIV水平，并且影响或控制偶尔能够在没有药物治疗的情况下控制HIV的个体的出现。在急性感染期间开始抗逆转录病毒治疗（ART）可能允许患者随后在没有ART的情况下控制HIV的观察结果也表明， 在急性感染期间手术。这些事件包括HIV特异性CD4细胞发育受损、抗原呈递缺陷和T细胞过度活化，以及T细胞产生和周转中断。项目3通过使用II类四聚体，以及通过细胞内细胞因子产生、ELISPOT和肽刺激的淋巴细胞增殖测量的对HIV肽基质的功能反应分析，在选定的一组深入研究的受试者中，在克隆水平上检查CD4细胞衰竭的免疫病理学。实验还将纳入参与项目1的患者的测量结果。我们将确定克隆是否被删除，使无能或仅部分响应，以及它们是否进入凋亡途径。本项目还将探讨抑制 CD4应答HIV包膜抗体的gp120，逃逸的特异性中和抗体在早期感染，以及这种逃逸是否受到功能性HIV特异性CD4细胞的存在的影响。

Immune responses and pathogenic events resulting from high viral replication during acute HIV infection determine the levels of HIV in late infections, and effect or control the emergence of occasional individuals who are able to control HIV without drug therapy. Observations that the initiation of antiretroviral therapy (ART) during acute infection may permit patients to subsequently control HIV without ART also indicate that critical pathogenic events are operative during acute infection. These events include impaired development of HIV-specific CD4 cells, defective antigen presentation, and hyperactivation of T cells with disruptions in T cell production and turnover. Project 3 examines the immunopathology of CD4 cell failure at the clonal level in a selected group of intensively studied subjects, through the use of class II tetramers, and an analysis of functional responses to HIV peptide matrixes as measured by intracellular cytokine production, ELISPOT, and peptide-stimulated lymphocyte proliferation. The experiments also will incorporate measurements obtained in patients participating in project 1. We will determine whether clones are deleted, rendered anergic or only partially responsive, and whether they are entering an apoptosis pathway. This project will also explore the inhibition of CD4 responses to HIV envelope by antibodies to gp120, the specificity of escape from neutralizing antibody in early infection, and whether this escape is influenced by the presence of functional HIV-specific CD4 cells.