HIV INFECTION/IMMUNITY IN THE FEMALE REPRODUCTIVE TRACT

女性生殖道中的艾滋病毒感染/免疫

• 批准号: 6632140
• 负责人: ALexandria L. Howell
• 金额: $ 27.63万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6632140
• 关键词: HIV infections; T lymphocyte; biopsy; cell type; cellular immunity; chemokine; clinical research; communicable disease transmission; cytokine; cytokine receptors; disease /disorder proneness /risk; female; female reproductive system; heterosexuals; hormone regulation /control mechanism; human immunodeficiency virus 1; human subject; menstrual cycle; mucosal immunity; receptor expression; sex hormones; tissue /cell culture; women's health

DESCRIPTION: (Adapted from abstract) This is a revised proposal that seeks to evaluate the infectability of various cell types within the female reproductive tract and mucosal immune responses that might potentially protect against infection. The heterosexual transmission of HIV-1 is the primary mechanism for the infection of women. Various types of FRT cells are potential targets for infection, and a better understanding of the interaction of these cells with HIV-1 is important for the rational design of antiviral therapeutics and in the evaluation of mucosal vaccines. The P.I. has demonstrated that several FRT cell types are susceptible to infection with primary isolates of HIV-1. Preliminary work has led to the formulation of a set of hypotheses to be tested: 1) The susceptibility of FRT cells to HIV-1 infection is dependent on sex hormone and cytokine status and on chemokine and chemokine co-receptor expression, all of which may vary with the menstrual cycle and 2) That the functional properties of immune cells within the FRT are controlled by sex hormones and cytokines. To address these hypotheses, the P.I. proposes a systematic study using cells and tissues obtained from the FRT of HIV-1 seronegative women to define conditions that influence the infectivity of FRT cells by HIV-1. The effects of sex hormones and immune cytokines, as well as the effects of chemokine and chemokine co-receptor expression by FRT cells, on the susceptibility to HIV-1 infection will be examined. Additionally, the influence of sex hormones and immune cytokines on responses to recall antigens, as well as the mechanisms by which sex hormones and cytokines regulate FRT T cell responses will be defined. Data from these studies will increase our understanding of potential viral and immunologic factors that affect the heterosexual acquisition of HIV-1 infection by women, will be useful in developing approaches to reduce the susceptibility of women to HIV and other STDs, and will provide information important to the development of more effective mucosal vaccines.

描述：（改编自摘要）这是一项修订后的提案， 旨在评估体内各种细胞类型的感染性 女性生殖道和粘膜免疫反应可能 潜在地防止感染。异性传播 HIV-1是女性感染的主要机制。各种类型 的 FRT 细胞是潜在的感染目标，并且更好的 了解这些细胞与 HIV-1 的相互作用非常重要 用于抗病毒治疗的合理设计和评估 粘膜疫苗。 P.I.已经证明了一些 FRT 单元 类型易感染 HIV-1 初级分离株。 初步工作导致了一系列假设的形成 待测试： 1) FRT细胞对HIV-1感染的易感性为 依赖于性激素和细胞因子状态以及趋化因子和 趋化因子辅助受体的表达，所有这些都可能随 月经周期和 2) 免疫细胞的功能特性 FRT 内的激素由性激素和细胞因子控制。 为了解决这些假设，P.I.提出了一项系统研究，使用 从 HIV-1 血清阴性女性的 FRT 中获得的细胞和组织 定义影响 HIV-1 FRT 细胞感染性的条件。 性激素和免疫细胞因子的作用以及作用 FRT细胞趋化因子和趋化因子辅助受体表达的影响 将检查对 HIV-1 感染的易感性。此外， 性激素和免疫细胞因子对回忆反应的影响 抗原，以及性激素和细胞因子的机制 调节 FRT T 细胞反应将被定义。这些研究的数据 将增加我们对潜在病毒和免疫学的了解 影响异性性行为获得 HIV-1 感染的因素 妇女，将有助于制定减少 妇女对艾滋病毒和其他性病的易感性，并将提供 对于开发更有效的粘膜很重要的信息 疫苗。

项目成果

Synergy between IL-8 and GM-CSF in reproductive tract epithelial cell secretions promotes enhanced neutrophil chemotaxis.

IL-8 和 GM-CSF 在生殖道上皮细胞分泌中的协同作用可促进中性粒细胞趋化性增强。

• DOI: 10.1016/j.cellimm.2004.08.004
• 发表时间: 2004
• 期刊: Cellular immunology.
• 作者: Shen,Li;Fahey,JohnV;Hussey,StephenB;Asin,SusanaN;Wira,CharlesR;Fanger,MichaelW
• 通讯作者: Fanger,MichaelW