CELLULAR TRAFFICKING TO INFLAMED FEMALE GENITAL MUCOSA

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Pelvic inflammatory disease, tubal infertility and ectopic pregnancy typically emerge in females after a chronic infection with Chlamydia trachomatis or Neisseria gonorrhoeae. Due to the insidious nature of chlamydial infections, efforts have been put forth to develop a vaccine that would enhance the clearance of organisms, avoid chronic infections, and in turn, eliminate reproductive disability. Based on the theory of a common mucosal immune system, lymphocyte recruitment to the genital mucosa is predicted to occur when lymphocytes are activated at distant mucosal surfaces. Studies of Chlamydia genital infection in the mouse have shown that T cells are required for protection and effector T cells are found in the genital mucosa following immunization at other mucosal sites. Currently, the degree of T cell migration to the genital mucosa following antigen delivery at other mucosal surfaces is unknown in humans. In this proposal, we will test the hypothesis that T cells activated at other mucosal surfaces can be recruited to the genital mucosa during an inflammatory process. Since T cells are not commonly recruited to the genital mucosa, we will study females infected with C. trachomatis or N. gonorrhoeae as a model to test this hypothesis. The specific aims of this proposal are to: 1) Develop a method to identify T cells that home to the genital mucosa in vivo using individuals with a sexually transmitted disease (STD). 2) Determine if immunization by a distant mucosal route promotes T cell trafficking to the genital mucosa. We will define the homing receptor expression pattern (gut mucosal, other mucosal, non-mucosal) on endocervical T cells and IFNgamma+ peripheral blood cells from STD infected volunteers using flow cytometric techniques. We will also determine which adhesion molecules are induced within the female genital mucosa during STD infection by utilizing an in vitro fallopian tube culture of living tissue followed by immunohistological staining. The candidate homing receptor: adhesion molecule pairs will be tested in a genital mucosa adhesion assay. The frequency of genital mucosa homing T cells and mature dendritic cells will be monitored in volunteers following immunization with Salmonella typhi vaccine via different routes. These studies will contribute to the design of STD vaccines that would provide lasting immunity in the female genital mucosa.