Decidual CD4 Effector Memory and Resident Memory T Cells Respond to Cord Blood Allo‐Antigens

ABSTRACT Problem Maternal CD4 T cells are critical coordinators of maternal–fetal immune tolerance and immunity during pregnancy. Decidual regulatory T cells (T REG ) have been shown to provide essential immune suppressive functions to control allogeneic responses and inflammation. Activated CD4 memory T cells form the largest fraction of decidual T cells, yet their diversity, specificity, and functions remain largely undefined. Method of Study Using high‐dimensional flow cytometry (HDFC), computational and functional analysis to characterize decidual CD4 memory T‐cell types and their functions. Results Two types of decidual CD4 T cells, the effector memory cells (T EM ), and CD69+ PD1+ resident memory cells (T RM ) with a strong capacity to respond to cord blood allo‐antigens were identified. Important differences were found in their phenotypic, cytotoxic, and cytokine profiles that were dependent on fetal sex, mode of delivery, and human cytomegalovirus (HCMV) serology. Conclusions Thus, decidual CD4 T EM and T RM have unique immune effector functions and the ability to recognize and respond to fetal cord blood. This suggests that decidual CD4 T EM and T RM cells can recognize fetal allo‐antigens and, when not adequately controlled, may contribute to placental inflammation. Further definition of decidual T EM and CD69+ PD1+ T RM immune effector functions and specificity has clinical significance to define essential drivers of healthy pregnancy and pregnancy complications.