The contribution of Chlamydia-specific CD8⁺ T cells to upper genital tract pathology.

Abstract

Genital chlamydial infections lead to severe upper reproductive tract pathology in a subset of untreated women. We demonstrated previously that TNF-α producing CD8+ T cells contribute significantly to chlamydial upper genital tract pathology in female mice. Additionally, we observed minimal chlamydial oviduct pathology develops in OT-1 transgenic (OT-1) mice, wherein CD8+ T cell repertoire is restricted to recognition of the ovalbumin peptide Ova257–264, suggesting that non-Chlamydia-specific CD8+ T cells may not be responsible for chlamydial pathogenesis. In the current study, we evaluated whether antigen-specific CD8+ T cells mediate chlamydial pathology. Groups of wild type C57BL/6J (WT), OT-1 mice, and OT-1 mice replete with WT CD8+ T cells (1×106 cells/mouse intravenously) were infected intravaginally with C. muridarum (5 × 104 IFU/mouse). Serum total anti-Chlamydia antibody and total splenic anti-Chlamydia IFN-γ and TNF-α responses were comparable among the three groups of animals. However, Chlamydia-specific IFN-γ and TNF-α production from purified splenic CD8+ T cells of OT-1 mice was minimal, whereas responses in OT-1 mice replete with WT CD8+ T cells were comparable to those in WT animals. Vaginal chlamydial clearance was comparable between the three groups of mice. Importantly, the incidence and severity of oviduct and uterine horn pathology was significantly reduced in OT-1 mice but reverted to WT levels in OT-1 mice replete with WT CD8+ T cells. Collectively, these results demonstrate that Chlamydia-specific CD8+ T cells contribute significantly to upper genital tract pathology.