Project 3 - MBSR & the Immune System in Early HIV Infection

项目3的总体目标是测试关于感知压力和情绪在早期HIV感染期间改变HIV相关免疫功能的机制的假设。压力和抑郁情绪与CD4细胞计数的快速下降有关，CD4细胞计数是艾滋病毒疾病进展的关键免疫终点。最近的证据表明，受神经内分泌系统影响的几种可能的生物学机制是HIV疾病进展的潜在重要因素：(1)CCR5和CXCR4受体表达增加。这些HIV细胞进入的共受体部分受自主神经系统的调节，这些共受体表达的增加可能促进HIV细胞进入和复制。(2) CD8 T细胞活化增加，这与更多的

The overall aim of Project 3 is to test hypotheses about mechanisms through which perceived stress and mood alter HIV-related immune function during early HIV infection. Stress and depressed mood are associated with more rapid declines in CD4 cell counts, the key immunologic endpoint through which disease progress occurs in HIV. Recent evidence suggests several plausible biological mechanisms that are influenced by the neuroendocrine system and are potentially important factors in HIV disease progression: (1) Increased CCR5 and CXCR4 receptor expression. These co-receptors for HIV cell entry are regulated in part by the autonomic nervous system and increased expression of these co-receptors may facilitate HIV cell entry and replication. (2) Increased CD8 T cell activation, which is strongly linked to more rapid loss of CD4 T cells. (3) Changes in cytokine expression and decreased NK cell function and plasmacytoid dendritic cells (PDC) that impair immune responses to HIV. For this project we will study in detail immune function and phenotype in a subset of 120 participants from the randomized, controlled trial of Mindfulness Based Stress Reduction (MBSR) in early HIV infection (Project 1 of this application). Data from neuroendocrine and autonomic nervous system (ANS) studies (Project 2) will be linked to data from the immune assays performed in this study (Project 3) to define further the pathways through which perceived stress and mood influence the immune system in early HIV via the neuroendocrine system. Studying these pathways will advance our understanding of mind-body interactions in HIV and the mechanisms through which interventions such as MBSR may affect immune function in general and HIV disease progression in particular. We will test hypotheses that higher perceived stress and depressed mood at baseline are associated with higher CCR5 and CXCR4 receptor expression on CD4+ T cells (co-receptors for HIV entry), higher CD8 T cell activation, less advantageous cytokine levels, and lower levels of NK and PDC cells, and that decreases in stress and depression will predict improvement in each of these parameters. We will also test whether MBSR improves each of these immune parameters, and whether changes are linked with hypothesized neuroendocrine influences.