Sexually transmitted infection with Chlamydia trachomatis may lead to fibrotic blockage in women's upper genital tracts, resulting in tubal infertility. Intravaginal inoculation with C. muridarum readily induces fibrotic blockage or hydrosalpinx in mice and is used for investigating C. trachomatis pathogenicity. Using this model in combination with an antibody depletion approach, we confirmed CD4⁺ T cell-mediated protective immunity and a CD8⁺ T cell-dependent pathogenic mechanism during chlamydial infection in C57BL/6J mice. However, when mice genetically deficient in CD8⁺ T cells were evaluated, we found, surprisingly, that these mice were still able to develop robust hydrosalpinx following C. muridarum infection, both contradicting the observation made in C57BL/6J mice and suggesting a pathogenic mechanism that is independent of CD8⁺ T cells. We further found that depletion of CD4⁺ T cells from CD8⁺ T cell-deficient mice significantly reduced chlamydial induction of hydrosalpinx, indicating that CD4⁺ T cells became pathogenic in mice genetically deficient in CD8⁺ T cells. Since depletion of CD4⁺ T cells both promoted chlamydial infection and reduced chlamydial pathogenicity in CD8⁺ T cell-deficient mice, we propose that in the absence of CD8⁺ T cells, some CD4⁺ T cells may remain protective (as in C57BL/6J mice), while others may directly contribute to chlamydial pathogenicity. Thus, chlamydial pathogenicity can be mediated by distinct host mechanisms, depending upon host genetics and infection conditions. The CD8⁺ T cell-deficient mouse model may be useful for further investigating the mechanisms by which CD4⁺ T cells promote chlamydial pathogenicity.

Heze Yu

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