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

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.