CD200-CD200R expression and chronic immune activation in HIV infection

描述（由申请人提供）：在这个试点提案中，我们将解决CD200和CD200R在HIV感染个体中失调的假设。CD200和CD200R是T细胞调控单核细胞、巨噬细胞和树突状细胞功能的重要途径。该通路的触发已被证明可以直接抑制单核细胞和巨噬细胞的激活，从而降低T细胞的激活。在本提案的目标1中，我们将进行初步研究，以表征CD200在T细胞上的表达及其与不同感染阶段HIV感染者慢性免疫激活的关系。在Aim 2中，我们将检查CD200受体CD200R在HIV感染者骨髓系细胞上的表达。我们还将研究骨髓系细胞中的CD200R表达与T细胞上的慢性激活标记物以及血浆中脂多糖水平之间的关系。在HIV感染者中，CD200或CD200R（或两者都有）调节的改变可能直接影响慢性免疫激活，因此评估这一途径的每个部分是很重要的。如果成功，这些结果将为未来的研究铺平道路，旨在直接研究CD200/CD200R通路对慢性免疫激活的机制作用，以及废除或促进CD200R信号作为治疗策略的手段。

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. 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.