FACTORS AFFECTING VAGINAL IMMUNOLOGY AND HIV 1 INFECTION

影响阴道免疫和 HIV 1 感染的因素

• 批准号: 2206617
• 负责人: Deborah J Anderson
• 金额: $ 22.92万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-05-01 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2206617
• 关键词: HIV infections; cell mediated lymphocytolysis test; cervical /vaginal smear; enzyme linked immunosorbent assay; estrogens; female; hormone regulation /control mechanism; human immunodeficiency virus; human subject; immunoglobulin A; immunoglobulin G; immunoglobulin M; menstrual cycle; mucosal immunity; polymerase chain reaction; postpartum; pregnancy; semen; sex behavior; tissue /cell culture; vagina; virus infection mechanism

The human vagina is a principal entry and transmission site for sexually transmitted pathogens including HIV-1, yet little information is available concerning influences of endogenous and exogenous factors on vaginal mucosal immune defense mechanisms or other parameters affecting vaginal infection. We propose to test the hypothesis that reproductive hormones, intercourse and intravaginal products affect the transmission rate of HIV- 1 through alterations in vaginal defense mechanisms, specifically by: l) inhibition of vaginal humoral, cellular or innate immune defense mechanisms; 2) enhancement of susceptibility to pathogen infection through improved access to target cells and/or their activation, and/or 3) enhancement of HIV-1 production through activation of infected cells in the vagina. RT-PCR, ELISA and immunohistology techniques will be utilized to better define immune defense mechanisms of the normal human vagina. Lymphocyte and inflammatory cell populations, and their products (immunoglobulins, cytokines, activation and adhesion molecules) will be assessed in surgical specimens from various regions of the vagina and cervicovaginal lavage specimens (CVLs) obtained: 1) throughout the menstrual cycle, 2) throughout pregnancy and the postpartum period, 3) post menopause with and without estrogen replacement, 4) following intercourse or administration of seminal components, and 5) following administration of intravaginal products. Similar CVL data will be attained for HIV-1 infected women (WITS cohort) and correlated with HIV-1 titers in CVLs assessed by quantitative HIV culture and PCR methods. In addition, studies will be performed to further document effects of cervicovaginal secretions, taken from the conditions listed above, on immune function and HIV-1 infectivity in vitro. This study is designed to provide a foundation for the development of vaccines and other strategies against sexually transmitted pathogens.

人类阴道是性行为的主要条目和传输站点 传播病原体在内，包括HIV-1，但很少有信息 关于内源性和外源性因素对阴道的影响 粘膜免疫防御机制或其他影响阴道的参数 感染。我们建议测试生殖激素， 性交和阴道内产物影响HIV的传播率 1通过改变阴道防御机制，特别是：l） 抑制阴道体液，细胞或先天免疫防御 机制； 2）通过 改善了对目标细胞和/或其激活的访问，/或3） 通过激活感染细胞在 阴道。 RT-PCR，ELISA和免疫组织学技术将被利用 更好地定义正常人阴道的免疫防御机制。 淋巴细胞和炎症细胞群体及其产物 （免疫球蛋白，细胞因子，激活和粘附分子）将是 在阴道各个区域的手术标本中进行评估 获得的子宫颈灌洗标本（CVL）：1） 月经周期，2）在整个怀孕和产后期间，3） 更年期后有或没有雌激素替代，4）以下 性交的性交或给药，5）以下 阴道内产物的给药。将获得类似的CVL数据 用于HIV-1感染的女性（WITS队列），并与HIV-1滴度相关 通过定量HIV培养和PCR方法评估的CVL。此外， 将进行研究以进一步记录子宫颈阴道的影响 分泌物，从上述条件，免疫功能和 HIV-1体外感染性。这项研究旨在提供基础 为了开发疫苗和其他针对性的策略 传播病原体。