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Background:  Adaptive immune responses that mediate protection against  Chlamydia trachomatis  (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.   Methods:  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.   Results:  A CD4 + TNF-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 CD4 + IFN-γ response was detected more often in women without vs. with reinfection (60 vs. 33%,  P  = 0.005).   Conclusions:  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.

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