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

项目3-MBSR

• 批准号: 6884431
• 负责人: JAY A LEVY
• 金额: $ 17.85万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6884431
• 关键词: HIV infections; T lymphocyte; alternative medicine; autonomic nervous system; behavioral /social science research tag; chemokine receptor; dendritic cells; emotions; enzyme linked immunosorbent assay; human tissue; immune response; meditation; natural killer cells; neuroendocrine system; pathologic process; perception; phenotype; psychoneuroimmunology; psychophysiology; receptor expression; stress; stress management

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.

项目 3 的总体目标是检验有关在早期 HIV 感染期间感知压力和情绪改变 HIV 相关免疫功能的机制的假设。压力和抑郁情绪与 CD4 细胞计数更快下降有关，CD4 细胞计数是 HIV 疾病进展的关键免疫学终点。最近的证据表明，几种可能的生物学机制受到神经内分泌系统的影响，并且是 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 细胞进入的辅助受体部分受到自主神经系统的调节，这些辅助受体表达的增加可能会促进 HIV 细胞的进入和复制。 (2) CD8 T 细胞活化增加，这与更多 CD4 T 细胞快速损失。 (3) 细胞因子表达的变化以及 NK 细胞功能和浆细胞样树突状细胞 (PDC) 的降低，损害对 HIV 的免疫反应。在这个项目中，我们将详细研究早期 HIV 感染中基于正念的减压 (MBSR) 随机对照试验（本申请的项目 1）中 120 名参与者的免疫功能和表型。神经内分泌和自主神经系统 (ANS) 研究（项目 2）的数据将与本研究（项目 3）中进行的免疫测定的数据联系起来，以进一步确定感知压力和情绪影响早期 HIV 免疫系统的途径通过神经内分泌系统。研究这些途径将增进我们对艾滋病毒身心相互作用及其机制的理解 MBSR 等干预措施可能会影响一般免疫功能，特别是艾滋病毒疾病进展。我们将测试以下假设：基线时较高的感知压力和抑郁情绪与 CD4+ T 细胞（HIV 进入的共同受体）上较高的 CCR5 和 CXCR4 受体表达、较高的 CD8 T 细胞激活、较不利的细胞因子水平以及较低的细胞因子水平相关。 NK 和 PDC 细胞，以及压力和抑郁的减少将预测这些参数中的每一个的改善。我们还将测试 MBSR 是否改善了这些免疫参数，以及变化是否与假设的神经内分泌影响有关。