The immunopathogenesis of Chlamydia trachomatis-induced oviduct pathological sequelae is not well understood. Mice genetically deficient in perforin (perforin-/- mice) or tumor necrosis factor alpha (TNF-α) production (TNF-α-/- mice) displayed comparable vaginal chlamydial clearance rates but significantly reduced oviduct pathology (hydrosalpinx) compared to that of wild-type mice. Since both perforin and TNF-α are effector mechanisms of CD8+ T cells, we evaluated the role of CD8+ T cells during genital Chlamydia muridarum infection and oviduct sequelae. Following vaginal chlamydial challenge, (i) mice deficient in TAP I (and therefore the major histocompatibility complex [MHC] I pathway and CD8+ T cells), (ii) wild-type mice depleted of CD8+ T cells, and (iii) mice genetically deficient in CD8 (CD8-/- mice) all displayed similar levels of vaginal chlamydial clearance but significantly reduced hydrosalpinx, compared to those of wild-type C57BL/6 mice, suggesting a role for CD8+ T cells in chlamydial pathogenesis. Repletion of CD8-/- mice with wild-type or perforin-/-, but not TNF-α-/-, CD8+ T cells at the time of challenge restored hydrosalpinx to levels observed in wild-type C57BL/6 mice, suggesting that TNF-α production from CD8+ T cells is important for pathogenesis. Additionally, repletion of TNF-α-/- mice with TNF-α+/+ CD8+ T cells significantly enhanced the incidence of hydrosalpinx and oviduct dilatation compared to those of TNF-α-/- mice but not to the levels found in wild-type mice, suggesting that TNF-α production from CD8+ T cells and non-CD8+ cells cooperates to induce optimal oviduct pathology following genital chlamydial infection. These results provide compelling new evidence supporting the contribution of CD8+ T cells and TNF-α production to Chlamydiainduced reproductive tract sequelae.
ASJC Scopus subject areas
- Infectious Diseases