The Role of Regulatory T Cells in Determining Outcomes of Chlamydial Genital Tract Infection (164.15)

Abstract

Abstract Females are at risk for severe oviduct disease after genital tract infection with Chlamydia trachomatis. Previous studies in our laboratory demonstrate Toll-like receptor 2 (TLR2) activation plays an important role in the development of chronic oviduct pathology after murine chlamydial genital tract infection. Clearance of chlamydial infection has been shown in human and murine investigations to depend on IFN-γ-producing CD4+ T cells. However, an overly zealous adaptive T cell response may contribute to the development of chronic tissue pathology. Pathogen specific T effector cell responses can be suppressed by CD4+CD25+Foxp3+regulatory T cells (Tregs), whose suppressive activity may be abrogated by TLR2 activation. We hypothesize Chlamydia specific TLR2 activation abrogates Treg function resulting in an exacerbated adaptive immune response, which contributes to tissue pathology. Here, we successfully depleted Tregs in a Foxp3DTR mouse model by administration of diphtheria toxin prior to intravaginal infection with TLR2-stimulating Chlamydia murdarium. Although bacterial burden was unaltered, conditional ablation of Tregs resulted in increased IFN-γ-producing CD4+ and CD8+ T cells. Additional studies will determine if removal of Treg suppression leads to increased immunopathology.