T CELL-MEDIATED IMMUNITY IN CHLAMYDIAL GENITAL INFECTION

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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.