T CELL-MEDIATED IMMUNITY IN CHLAMYDIAL GENITAL INFECTION

描述（改编自申请人摘要）：沙眼衣原体 仍然是盆腔炎的主要原因，可能导致 输卵管阻塞和不孕症。虽然有效的抗生素 生殖道感染可能会上升到上生殖道， 在疾病被发现之前就已经有了严重的损害。一项适当的战略 是研制一种疫苗来预防感染和随后的病理。 在小鼠-MoPn模型中有充分的文献证明， 依赖于细胞免疫在小鼠-MoPn模型中， 感染、感染消退和对再感染的抵抗是 主要与CD 4 Th 1反应有关。提案重点是 引发和调节Th 1应答的机制 在生殖道中。CD 4细胞返回生殖器的机制 1）鉴定CD 4细胞上的归巢受体 和它们各自的内皮细胞配体（ECL）; 2）定义 归巢受体/ECL对负责粘附和迁移到 生殖道;和3）鉴定调节生殖道的细胞因子和趋化因子， ECL表达。由于鼠系统中对再感染的免疫力也是 T细胞依赖性，CD 4记忆细胞募集到生殖器的作用 道在保护对阴道衣原体挑战将是 测定生殖道攻毒感染后，既往 通过粘膜途径用活MoPn免疫导致保护性Th 1应答，而胃肠外免疫则激发非保护性Th 2 反应因此，保护性的CD 4 Th 1细胞引起 通过粘膜免疫被招募到生殖道， 确定，并与非保护性 通过肠胃外免疫引起的Th 2细胞被募集。的cd 4 由每种免疫途径引起的亚群将被确定，沿着 通过测定介导细胞凋亡的归巢受体/ECL对， 这些亚群在衣原体感染后被运送到生殖道， 挑战.

DESCRIPTION (Adapted from Applicant's Abstract): Chlamydia trachomatis remains a major cause of pelvic inflammatory disease which may lead to tubal obstruction and infertility. While effective antibiotics are available, the infection may ascend to the upper genital tract, causing significant damage before disease is recognized. An appropriate strategy is to develop a vaccine which prevents infection and subsequent pathology. It is well documented in the mouse-MoPn model that immunity to chlamydiae depends on cell mediated immunity. In the mouse-MoPn model of genital infection, resolution of infection and resistance to reinfection are primarily associated with CD4 Th 1 response. The proposal focuses on mechanisms which elicit and regulate the development of the Th 1 response in the genital tract. The mechanism by which CD4 cells home to the genital tract will be determined by: 1) Identifying homing receptors on CD4 cells and their respective endothelial cell ligands (ECL); 2) defining the homing receptor/ECL pairs responsible for adhesion and migration to the genital tract; and 3) identifying cytokines and chemokines which regulate ECL expression. Since immunity to reinfection in the murine system is also T cell dependent, the role of CD4 memory cell recruitment to the genital tract in the protection against vaginal chlamydial challenge will be determined. Upon challenge infection in the genital tract, prior immunization with live MoPn by mucosal routes results in a protective Th 1 response, while parenteral immunization elicits a non-protective Th 2 response. Thus, the mechanism by which protective CD4 Th 1 cells elicited by mucosal immunization are recruited to the genital tract will be determined, and contrasted with the mechanism by which the non-protective Th 2 cells elicited by parenteral immunization are recruited. The CD4 subsets elicited by each route of immunization will be determined, along with the determination of the homing receptor/ECL pairs which mediate trafficking of these subsets to the genital tract upon chlamydial challenge.