Effects of Menopause on T-cell Immunity in HIV-Infected Women

描述（由申请人提供）：全球艾滋病毒流行病在女性中迅速蔓延，需要进行额外的研究来检查可能独特地改变女性和男性之间艾滋病毒疾病过程的重要免疫差异。女性性激素，雌激素，是一种有效的细胞介导的免疫增强剂，驱动更有效的免疫反应，病原体和接种疫苗的妇女（与男性相比）。这项研究的总体目标是研究女性性激素对女性艾滋病毒免疫发病机制的影响。这项研究计划将检验这样一个假设，即绝经期，以雌激素急剧下降为标志，将导致免疫功能的变化，可能危及对艾滋病毒的免疫控制。一项回顾性纵向分析将被用来检查100名艾滋病毒感染妇女和50名艾滋病毒未感染妇女绝经的影响。本工作的具体目的是：1）研究绝经对HIV感染妇女T细胞功能的影响，包括抗原特异性反应和细胞增殖。我们还将量化功能上重要的T细胞亚群，包括T细胞成熟阶段，T细胞活化和调节性T细胞，2）通过比较50名未感染HIV的女性的相同免疫分析，区分绝经和年龄增长的全球免疫效应，区分HIV疾病状态对绝经相关免疫变化的影响。我们还将比较绝经对HIV疾病不同临床状态女性的免疫影响，如未经治疗的长期非进展者和经治疗的抗逆转录病毒应答者。如果成功的话，这项工作可以提供一个理论基础，进一步探索性激素对艾滋病毒免疫发病机制的影响或针对疾病病理生理学的适当干预措施的设计。预计到2015年，美国50%的艾滋病毒感染者将达到50岁或以上，因此这些发现可能与老年艾滋病毒感染妇女的护理有关。 公共卫生相关性：全球艾滋病毒流行病正在妇女中迅速蔓延，需要进行更多的研究，以检查可能独特地改变妇女艾滋病毒病程的重要免疫差异。雌性激素，雌激素，是一种免疫功能增强剂，驱动对病毒的强烈免疫反应。这项研究的目的是检查是否雌激素的损失与绝经期使艾滋病毒感染的妇女更难以对艾滋病毒进行免疫攻击。

DESCRIPTION (provided by applicant): The global HIV epidemic is spreading rapidly in women, and additional research is warranted to examine important immune differences that may uniquely alter the course of HIV disease between women and men. The female sex hormone, estrogen, is a potent enhancer of cell-mediated immunity that drives more effective immune responses to pathogens and vaccination in women (compared to men). The overall objective of this research proposal is to examine the influence of female sex hormones on HIV immunopathogenesis in women. This research proposal will test the hypothesis that menopause, marked by a precipitous decline in estrogen, will lead to changes in immune function that may compromise immunologic control of HIV. A retrospective longitudinal analysis will be used to examine effects of menopause in 100 HIV-infected women and 50 HIV- uninfected women. The specific aims of this work are 1) Investigate the effects of menopause on T-cell function in HIV infected women, including antigen specific responses and cellular proliferation. We will also quantify functionally important T-cell subpopulations including T-cell maturation stages, T-cell activation, and regulatory T cells, and 2) Distinguish the impact of HIV disease status on immune changes associated with menopause by comparing identical immune analyses in 50 HIV-uninfected women to distinguish global immune effects of menopause and advancing age from those that characterize HIV disease. We will also compare immune effects of menopause in women with different clinical states of HIV disease, such as untreated long term non-progressors and treated antiretroviral responders. If successful, this work could provide a rationale for further exploration of sex hormone influences on HIV immunopathogenesis or the design of appropriate interventions targeted at disease pathophysiology. It is expected that 50% of HIV-infected patients in the U.S. will be 50 years or older by 2015, thus these findings could be relevant to the care of aging HIV-infected women. PUBLIC HEALTH RELEVANCE: The global HIV epidemic is spreading rapidly in women, and additional research is needed to examine important immune differences that may uniquely alter the course of HIV disease in women. The female hormone, estrogen, is an enhancer of immune function that drives strong immune responses against viruses. The purpose of this study is to examine whether loss of estrogen with menopause makes it more difficult for the HIV-infected women to mount an immune attack against HIV.