An Adaptive -Specific IFN-γ-Producing CD4 T Cell Response Is Associated With Protection Against Chlamydia Reinfection in Women.

Adaptive immune responses that mediate protection against (CT) remain poorly defined in humans. Animal chlamydia models have demonstrated that CD4 Th1 cytokine responses mediate protective immunity against reinfection. To better understand protective immunity to CT in humans, we investigated whether select CT-specific CD4 Th1 and CD8 T cell cytokine responses were associated with protection against CT reinfection in women. Peripheral blood mononuclear cells were collected from 135 CT-infected women at treatment and follow-up visits and stimulated with CT antigens. CD4 and CD8 T-cells expressing IFN-γ, TNF-α, and/or IL-2 were assessed using intracellular cytokine staining and cytokine responses were compared between visits and between women with vs. without CT reinfection at follow-up. A CD4TNF-α response was detected in the majority (77%) of study participants at the treatment visit, but a lower proportion had this response at follow-up (62%). CD4 IFN-γ and CD4 IL-2 responses occurred less frequently at the treatment visit (32 and 18%, respectively), but increased at follow-up (51 and 41%, respectively). CD8 IFN-γ and CD8 TNF-α responses were detected more often at follow-up (59% for both responses) compared to the treatment visit (30% for both responses). At follow-up, a CD4IFN-γ response was detected more often in women without vs. with reinfection (60 vs. 33%, = 0.005). Our findings suggest that a CT-specific CD4 IFN-γ response is associated with protective immunity against CT reinfection and is thus an important component of adaptive immunity to CT in women.