Pelvic inflammatory disease due to Chlamydia trachomatis is an important cause of poor reproductive health for women. The pathogenesis for this disease is unclear and new knowledge in this area is needed to improve approaches for prevention and treatment. The overall goal of this proposal is to elucidate the cellular immune pathogenesis of C. trachomatis PID. Epidemiological data collected from a group of commercial sex workers in Nairobi, Kenya who have a high incidence of C. trachomatis cervical infection and pelvic inflammatory disease suggest that cellular immune responses to chlamydia infection are pivotal in determining the course of this infection. It was observed that among HIV infected women, CD4 cell loss dramatically increased the risk of C. trachomatis PID. As well, a specific HLA class I allele was independently associated with an increased risk of C. trachomatis PID. suggesting a role for CD8 T lymphocytes in mediating tissue inflammation. Based on these observations, the present grant proposes to continue to evaluate this cohort of commercial sex workers for incident C. trachomatis infection and PID cases- Between 300 and 600 women will be enrolled and an estimated 50 to 75 women with C. trachomatis PID and 200 women with uncomplicated cervical chlamydia infection will be evaluated for cellular immune responses. The study hypothesis is that CD4 T cells protect against C. trachomatis PID and that antigen specific CD8 T cells mediate the inflammatory damage to the upper reproductive tract. The cellular immune response in the reproductive tract among-women with PID will be characterized by collecting endometrial biopsy tissue and determining the immunophenotypes of lymphocytes infiltrating the endometrium and correlating this with cytokine/enzyme specific mRNA characteristic of the T cell subsets, CD4 TH1, TH2 and CD8 CTLs. Cervical scrape samples containing exudative lymphocytes will also have the cytokine/enzyme specific mRNA for T cell subsets determined for women with C. trachomatis cervical infection alone and compared to women with C. trachomatis PID. For both endometrial and cervical samples, RT-PCR will be used to characterize cytokine/enzyme mRNA patterns. In aggregate, the data will shed light on the role of CD8 cytotoxic T lymphocytes in the pathogenesis of C. trachomatis PID and the potential mechanisms by which CD4 T lymphocytes confer protection against C. trachomatis PID.
Showing the most recent 10 out of 75 publications
