CD200-CD200R expression and chronic immune activation in HIV infection

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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.