The roles of TGFb signaling in CD4 T cell responses to Chlamydia infection in the female reproductive tract 9284

Abstract Description CD4 T cells are essential for host immunity to the intracellular bacterium Chlamydia, and the formation of tissue-resident memory CD4 T cells (CD4 TRM) in the female reproductive tract (FRT) is key for vaccine-induced protective immunity. As shown in previous studies, the pleiotropic cytokine transforming growth factor beta (TGFβ) regulates T cell migration, effector function, and memory maintenance in a context-dependent manner. To investigate the role of TGFβ signaling during Chlamydia infection in the FRT, we co-transferred WT and Tgfbr2fl/fl dLck-cre (Tgfbr2-/-) CD4 T cells into Tcrβ-/- recipient mice and compared CD4 T cell responses following Chlamydia muridarum intravaginal infection. At day 14, the ratio of WT:Tgfbr2-/- KO CD4 T cells was much higher in the FRT than in the draining iliac lymph nodes (DLNs), indicating that TGFβ signaling promotes CD4 T cell migration/homing to the FRT during the effector phase. A similar trend was observed at a memory time point (56 dpi), with reduced CD69 expression in the Tgfbr2-/- CD4 T cell compartment, suggesting that TGFβ signaling is essential for CD4 TRM maintenance in the FRT. The reduced effector responses and memory maintenance in Tgfbr2-/- CD4 T cells resulted in poor protective immunity, as Tgfbr2-/- mice exhibited higher bacterial burden than WT during secondary C. muridarum infection. Together, these data support the critical roles of TGFβ signaling in CD4 T cells during acute bacterial infection at the FRT mucosa. Topic Categories Mucosal and Regional Immunology (MUC)