HIV INFECTION/IMMUNITY IN THE FEMALE REPRODUCTIVE TRACT

描述：（改编自摘要）这是一份修订后的提案， 旨在评估各种细胞类型的感染性， 女性生殖道和粘膜免疫反应， 可能防止感染。异性性传播 艾滋病毒-1是妇女感染的主要机制。各种类型 的FRT细胞是感染的潜在靶点， 了解这些细胞与HIV-1的相互作用是很重要的 用于抗病毒治疗的合理设计和评估 粘膜疫苗。私家侦探已经证明了几个FRT细胞 类型的人容易感染HIV-1的主要分离株。 初步工作导致提出了一套假设， 1）FRT细胞对HIV-1感染的易感性是 依赖于性激素和细胞因子状态以及趋化因子， 趋化因子共受体表达，所有这些都可能随着 月经周期和2）免疫细胞的功能特性 在FRT内，由性激素和细胞因子控制。 为了解决这些假设，P.I.提出了一个系统的研究， 从HIV-1血清阴性妇女的FRT中获得的细胞和组织， 定义影响HIV-1对FRT细胞感染性的条件。 性激素和免疫细胞因子的作用，以及 FRT细胞的趋化因子和趋化因子共受体表达， 将检查对HIV-1感染的易感性。另夕h 性激素和免疫细胞因子对回忆反应影响 抗原，以及性激素和细胞因子 调节FRT T细胞应答的术语将被定义。这些研究的数据 将增加我们对潜在的病毒和免疫学的理解， 影响异性性行为获得HIV-1感染的因素 将有助于制定办法， 妇女对艾滋病毒和其他性传播疾病的易感性，并将提供 信息重要的发展更有效的粘膜 疫苗。

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.