Pathogenic Mechanisms In HIV Disease

HIV感染患者的免疫系统以辅助/诱导（CD4） T淋巴细胞数量减少为特征。为了确定这些减少是继发于T细胞产生减少还是T细胞破坏增加，进行了一系列研究，其中使用体内DNA标记和体外ki67表达测量来研究T细胞周转率。ki67的表达水平未被发现与CD4+ T细胞的恢复程度相关，从而进一步支持了抗逆转录病毒治疗后CD4+ T细胞的扩增与免疫系统激活降低直接相关的假设。为了更好地了解HIV感染治疗后CD4+ T细胞恢复的本质，我们开展了一系列研究，利用CD62L （l -选择素）标记物对CD4+记忆（CD45+）进行功能表征。基于增殖模式、细胞因子产生和mRNA谱，发现CD62L+细胞具有中枢记忆细胞的特征，而CD62L-细胞具有效应记忆细胞的特征。在与分子微生物学实验室的合作研究中，我们能够证明SIV-HIV重组病毒V2区缺失与巨噬细胞嗜性增加有关。

The immune systems of patients with HIV infection are characterized by a decrease in the number of helper/inducer (CD4) T lymphocytes. In an effort to determine whether these decreases were secondary to decreased T cell production or increased T cell destruction, a series of studies were carried out in which rates of T cell turnover were studied using in vivo labeling of DNA and ex vivo measuremnt of ki67 expression. Levels of expression of ki67 werer found to correlate with the degree of CD4+ T cell recovery thus providing further suport to the hypotheseis that the expansisonsof CD4+ T cells seen following antiretroviral therapy are directly related to decreases in immune system activation. To better understand the nature of CD4+ T cell recovery following treatment of HIV infection, a series of studies were carried out to functionally characterize CD4+ memory (CD45+) using the marker CD62L (L-selectin). CD62L+ cells were found to have characteristics of central memory cells based upon patterns of proliferation, cytokine production and mRNA profiles while CD62L- cells were found to have characteristics of effector memory cells. In collaborative studies with the Laboratory of Molecular Microbiology we were able to demonstrate that deletions in the V2 region of SIV-HIV recombinant viruses were associated with an increase in macrophage tropism.