Cellular Immunity to Chlamydua at the Epithelial Interface

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DESCRIPTION (provided by applicant): Chlamydia trachomatis has a marked tissue tropism, replicating almost exclusively in epithelial cells lining the reproductive tract. The Chlamydia muridarum mouse model for human C. trachomatis disease has clearly demonstrated that T cells mediate protective immunity against reproductive tract infection. The central hypothesis of the grant is that Chlamydia-specific T cells responsible for sterilizing immunity interact with infected reproductive tract epithelial cells. Surprising little is known about T cell interactions with Chlamydia-infected epithelial cells. The major goal of the project is to understand which Chlamydia-specific T cell subsets eliminate infected epithelial cells from the reproductive tract, and how they accomplish that desired endpoint. Specifically the grant proposes to 1) To identify T cell subsets that interact with Chlamydia-infected oviduct epithelial cells to mediate sterilizing immunity, and identify the effector mechanism employed, 2) To define the specific antigen presentation pathways utilized by epithelial cells to present the Chlamydia antigens, 3) To determine the costimulatory and coinhibitory contributions of infected epithelial cells to activation of protective Chlamydia-specific T cells. To address these specific aims, unique oviduct epithelial cell lines have been generated to serve as antigen presenting cells for isolating Chlamydia- specific T cell lines. Understanding how T cells interact with infected epithelial cells to mediate sterilizing immunity may contribute to vaccine development by identifying surrogate markers for protective immunity that can be exploited in future vaccine trials. Chlamydia trachomatis infections of the reproductive tract have been the most commonly diagnosed bacterial STD in the United States since the early 1990's. In women, C. trachomatis infections commonly ascend into the Fallopian tubes causing infertility and ectopic pregnancies. Standard public health measures have not significantly decreased the incidence of C. trachomatis infections, therefore development of a Chlamydia vaccine would be a major step forward in public health. This grant proposes to contribute toward rational development of a Chlamydia vaccine by investigating how protective immunity works in the reproductive tract. Defining what protective T cells look like, and how they function, will be critical for designing and assessing future Chlamydia candidate vaccines.