T CELL-MEDIATED IMMUNITY IN CHLAMYDIAL GENITAL INFECTION

描述(摘自申请者摘要)：沙眼衣原体 仍然是盆腔炎的主要原因，这可能导致 输卵管阻塞和不孕症。虽然有效的抗生素是 如果可用，感染可能会上升到上生殖道，导致 在认识到疾病之前，造成重大损害。适当的战略 是开发一种预防感染和随后的病理的疫苗。 在小鼠MoPn模型中，对衣原体的免疫力已经得到了很好的证明 依赖于细胞免疫。在小鼠-MoPn生殖器模型中 感染、感染消退和对再感染的抵抗力 主要与CD4Th1应答有关。该提案的重点是 Th1应答的诱导和调控机制 在生殖道里。CD_4细胞寄生于生殖器的机制 途径将通过以下方式确定：1)识别CD4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对负责黏附和迁移到 生殖道；以及3)识别调节细胞因子和趋化因子 ECL表达。因为在小鼠系统中对再次感染的免疫力也 T细胞依赖、CD4记忆细胞向生殖器募集的作用 在保护阴道免受衣原体感染方面将受到挑战 下定决心。一旦生殖道受到挑战感染，优先 经粘膜途径接种活MoPn可产生保护性Th 1应答，而非肠道免疫引起非保护性Th2 回应。因此，保护性CD4Th1细胞诱导的机制 通过粘膜免疫被招募到生殖道 确定，并与非保护性的 对肠外免疫诱导的TH2细胞进行集落。人类免疫缺陷病毒 将确定由每条免疫路线引发的子集， 通过测定介导归巢的受体/ECL对 衣原体将这些亚群贩运到生殖道 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.