Chlamydia trachomatis is well-established as a major cause of sexually transmitted disease in the United States despite the availability of effective antibiotics. Infection in women commonly remains unnoticed but may then ascend the genital tract producing salpingitis and potentially tubal obstruction. While a strong immune response develops in humans to chlamydial genital infection, immunity to reinfection is apparently short- lived. The mechanism of this immunity and the reason for its short length are unknown. In animal models, both antibody and cell-mediated immunity (CMI) have been found to play important roles. CMI appears to be of major importance in the mouse, since B cell-deficient mice infected with the agent of mouse pneumonitis (MoPn) a C. trachomatis biovar, are able to resolve the infection in the same time frame as controls. This study will examine the role of different T cell subpopulations to determine their function in resolution of and resistance to chlamydial genital infection. Populations of spleen cells enriched for T cells bearing the L3T4 (helper/inducer) or Lyt 2 (cytotoxic/suppressor) surface markers will be injected into nude mice and their effect on the course of MoPn genital infection determined. Nude mice are normally unable to resolve a chlamydial infection and remain chronically infected. The antibody and CMI response of the recipient mice will be evaluated. Splenic T cell will be cultured with MoPn antigen, antigen processing cells, and interleukin 2 to select an antigen-specific T cell population. This population will be characterized and used to reconstitute nude mice. Furthermore, specific chlamydial outer membrane components including the major outer membrane protein, a 66 Kd protein, and lipopolysaccharide will be used to induce antigen-specific T cell clones. By use of this methodology, an insight may be gained into which chlamydial components bear epitopes responsible for eliciting a protective T cell response. Specific T helper cells will be generated which will stimulate only an IgA response to MoPn antigens in order to determine whether secretory antibody can contribute to immunity in the mouse. Finally, the role of gamma interferon will be investigated by the passive transfer of recombinant murine gamma interferon to infected nude mice and by the production of T cell clones secreting gamma interferon.
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