CD200-CD200R expression and chronic immune activation in HIV infection

描述（由申请人提供）：在本试验性提案中，我们将讨论HIV感染者中CD 200和CD 200 R失调的假设。 CD 200和CD 200 R形成了T细胞调节单核细胞、巨噬细胞和树突状细胞功能的关键途径。 已经显示触发该途径直接抑制单核细胞和巨噬细胞活化，这反过来降低T细胞活化。 在本提案的目标1中，我们将进行初步研究以表征T细胞上CD 200的表达及其与来自感染的各个阶段的HIV感染个体中的慢性免疫激活的关系。 在目标2中，我们将检测HIV感染个体的髓系细胞上的CD 200受体CD 200 R的表达。 我们还将研究髓系细胞上的CD 200 R表达与T细胞上的慢性活化标志物以及血浆中的脂多糖水平之间的关系。 HIV感染者中CD 200或CD 200 R（或两者）调节的改变可能直接影响慢性免疫激活，因此评估途径的每个部分非常重要。 如果成功的话，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CD 200/CD 200 R通路对慢性免疫激活的机制作用，以及作为一种治疗策略消除或促进CD 200 R信号传导的手段。

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.