Suppression of Chlamydial Pathogenicity by Nonspecific CD8⁺T Lymphocytes

Abstract

Chlamydia trachomatis, a leading infectious cause of tubal infertility, induces upper genital tract pathology such as hydrosalpinx, which can be modeled with Chlamydia muridarum infection in mice. Following C. muridarum inoculation, wild type mice develop robust hydrosalpinx but OT1 mice fail to do so because their T cell receptors are engineered to recognize a single ovalbumin epitope (OVA457-462). These observations have demonstrated a critical role of Chlamydia-specific T cells in chlamydial pathogenicity. In the current study, we have also found that OT1 mice can actively inhibit chlamydial pathogenicity. First, depletion of CD8+ T cells from OT1 mice led to the induction of significant hydrosalpinx by Chlamydia, indicating that CD8+ T cells are necessary to inhibit chlamydial pathogenicity. Second, adoptive transfer of CD8+ T cells from OT1 mice to CD8 knockout mice significantly reduced chlamydial induction of hydrosalpinx, demonstrating that OT1 CD8+ T cells are sufficient for attenuating chlamydial pathogenicity in CD8 knockout mice. Finally, CD8+ T cells from OT1 mice also significantly inhibited hydrosalpinx development in wild type mice following an intravaginal inoculation with Chlamydia. Since T cells in OT1 mice are engineered to recognize OVA457-462 epitope only, the above observations have demonstrated a chlamydial antigen-independent immune mechanism for regulating chlamydial pathogenicity. Further characterization of this mechanism may provide information for developing strategies to reduce infertility-causing pathology induced by infections.

Protective anti-chlamydial vaccine regimen-induced CD4+ T cell response mediates early inhibition of pathogenic CD8+ T cell response following genital challenge

“…Moreover, repletion of TNF-α +/+ CD8 + T cells in CD8 gene deficient mice restores the pathology comparable to wild type animals (Murthy et al 2011 ). Consistently, Guangming et al (Xie et al 2020 ) demonstrated that CD8 + T cells from OT1 mice also significantly inhibited hydrosalpinx development in wild-type mice following an intravaginal inoculation with Chlamydia. They conclude the hydrosalpinx-inhibitory CD8 + T cells are Chlamydia nonspecific or independent of chlamydial antigen recognition.…”