IMMUNITY TO CHLAMYDIAL GENITAL INFECTION

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DESCRIPTION (Adapted from the Applicant's Abstract): Chlamydia trachomatis is possibly the most common sexually transmitted bacterial pathogen in the world. In the United States, 4 million new cases of C, trachomatis urogenital tract infection occur each year, and it is estimated that the cost of treating those infections approaches $4 billion annually. Urogenital infections caused by C. trachomatis result in a number of diverse clinical conditions. Infections in women range from acute self-limiting infections to more serious infections that result in pelvic inflammatory disease, infertility and ectopic pregnancy. Considerable progress has been made in the past few years to significantly broaden our understanding of immune responses that develop during the course of chlamydial infection. However, our understanding of effector mechanisms that limit chlamydial infection and prevent reinfection is insufficient. The investigator's recent data suggest that both CD4+ T cells and B cells (antibody) contribute to adaptive immunity to chlamydial genital tract infection. Thus the overall goal of this project is to use the murine model of C. trachomatis genital tract infection to study the relationship between CD4+ T cells and antibody in adaptive immunity to infection. That goal will be realized through the studies described in 4 specific aims: 1) To determine the ability of immune B cells and antibody to reconstitute protective immunity in CD4-depleted B cell deficient mice; 2) To determine if the lack of mature B cells in B cell gene knockout mice affects the development of chlamydial-specific memory T cell responses; 3) To determine the effect of simultaneous immune cell depletions on acquired immunity; and 4) To evaluate the inhibitory effects of antibodies and lymphocytes on chlamydial growth in vitro (antibody dependent cellular cytotoxicity). These studies will broaden our understanding of how the host resists chlamydial infection, and may provide new insights into the formulation and administration of an effective vaccine to control the spread of chlamydial infections or prevent the serious sequelae of disease pathogenesis.