CD200-CD200R expression and chronic immune activation in HIV infection

描述(由申请人提供)：在这个试点方案中，我们将解决CD200和CD200R在HIV感染者中调控失调的假设。CD200和CD200R是T细胞调节单核细胞、巨噬细胞和树突状细胞功能的重要途径。这一途径的触发已被证明直接抑制单核细胞和巨噬细胞的激活，进而减少T细胞的激活。在本方案的目标1中，我们将进行初步研究，以确定不同感染阶段的HIV感染者T细胞上CD200的表达及其与慢性免疫激活的关系。在目标2中，我们将检测CD200受体CD200R在HIV感染者髓系细胞上的表达。我们还将研究CD200R在髓系细胞上的表达与T细胞上的慢性激活标志物以及血浆中脂多糖水平的关系。在HIV感染者中，CD200或CD200R(或两者)调节的改变可能直接影响慢性免疫激活，因此评估该途径的每一部分是重要的。如果成功，这些结果将为未来的研究铺平道路，这些研究旨在直接研究CD200/CD200R通路对慢性免疫激活的机制影响，并为取消或促进CD200R信号作为一种治疗策略提供手段。 公共卫生相关性：免疫激活是艾滋病毒疾病进展的主要驱动因素。这项研究将在HIV感染的背景下研究控制单核细胞、巨噬细胞和树突状细胞激活的一个潜在途径，即CD200-CD200R途径。我们将确定CD200和CD200R的表达是否存在缺陷，可能导致HIV疾病免疫活性增强。

DESCRIPTION (provided by applicant): In this pilot proposal, we will address the hypothesis that CD200 and CD200R are dysregulated in HIV infected individuals. CD200 and CD200R form a critical pathway by which monocyte, macrophage, and dendritic cell function can be regulated by T cells. Triggering of this pathway has been shown to directly suppress monocyte and macrophage activation, which in turn reduces T cell activation. In Aim 1 of this proposal we will perform the initial studies to characterize the expression of CD200 on T cells and its relatio to chronic immune activation in HIV infected individuals from various stages of infection. In Aim 2 we will examine expression of the receptor for CD200, CD200R, on cells of the myeloid lineage in HIV infected individuals. We will also examine the relationship between CD200R expression on myeloid lineage cells and chronic activation markers on T cells, as well as lipopolysaccharide levels in the plasma. Altered regulation of either CD200 or CD200R (or both) in HIV infected individuals could directly influence chronic immune activation, so it is important to assess each part of the pathway. If successful, these results will pave the way to future studies designed to directly study the mechanistic effects of the CD200/CD200R pathway on chronic immune activation, as well as a means to either abrogate or promote CD200R signaling as a therapeutic strategy. PUBLIC HEALTH RELEVANCE: Immune activation is a primary driver of HIV disease progression. This study will examine one potential pathway that controls activation of monocytes, macrophages, and dendritic cells, the CD200-CD200R pathway, in the context of HIV infection. We will determine whether there are defects in the expression of CD200 and CD200R that could lead to heightened immune activation in HIV disease.