Cytotoxic CD4+T Cells Are Induced during Infection with Chlamydia trachomatis

Chlamydia trachomatis is the most common cause of bacterial sexually transmitted infection in both men and women. Immunity to C. trachomatis involves many cell types, but CD4+ + T cells play a key role in protecting the host during natural infection. Specifically, IFN-g g production by CD4+ + T cells is the main effector responsible for bacterial clearance, yet the exact mechanism by which IFN-g g confers protection is poorly defined. In our efforts to define the specific mechanisms for bacterial clearance, we now show that IFN-g g upregulates expression of MHC class II (MHCII) on nonhematopoietic cells during C. trachomatis infection in vivo. We also find that MHCII expression on epithelial cells of the upper genital tract contributes to the efficient clearance of bacteria mediated by pathogen-specific CD4+ + Th1 cells. As we further cataloged the protective mechanisms of C. trachomatis-specific- specific CD4+ + T cells, we found that the T cells also express granzyme B (GzmB) when coincubated with infected cells. In addition, during C. trachomatis infection of mice, primed activated-naive CD4+ + Th1 cells displayed elevated granzyme transcripts ( GzmA, GzmB, GzmM, GzmK, GzmC) ) compared with memory CD4+ + T cells in vivo. Finally, using intracellular cytokine staining and a GzmB-/-- /- mouse strain, we show that C. trachomatis-specific- specific CD4+ + Th1 cells express GzmB upon Ag stimulation, and that this correlates with Chlamydia clearance in vivo. Together these results have led us to conclude that Chlamydia-specific specific CD4+ + Th1 cells develop cytotoxic capacity through engagement with nonhematopoietic MHCII, and this correlates to C. trachomatis clearance. The Journal of Immunology, , 2024, 213: 328-338.- 338.