Fetal antigen available during pregnancy induces the proliferation of maternal T cells. It is unknown， however， whether these antigen-activated T cells differentiate into long-lived memory T cells that are capable of mediating rapid-recall responses to tissue antigens. To test the hypothesis that pregnancy induces an alternative fate in fetal-specific maternal T cells， we used a murine model to track longitudinally fetal-specific T cells in pregnant and postpartum animals and test the response of these cells when challenged with the same antigen during sequential pregnancy or skin transplantation. Fetal-specific CD8 T cells were robustly primed during pregnancy but failed to acquire robust effector functi... More
Fetal antigen available during pregnancy induces the proliferation of maternal T cells. It is unknown， however， whether these antigen-activated T cells differentiate into long-lived memory T cells that are capable of mediating rapid-recall responses to tissue antigens. To test the hypothesis that pregnancy induces an alternative fate in fetal-specific maternal T cells， we used a murine model to track longitudinally fetal-specific T cells in pregnant and postpartum animals and test the response of these cells when challenged with the same antigen during sequential pregnancy or skin transplantation. Fetal-specific CD8 T cells were robustly primed during pregnancy but failed to acquire robust effector functions. These primed cells persisted long term in postpartum animals， frequently maintained a programmed death 1 (PD-1) phenotype， and failed to expand or produce cytokines robustly in response to second pregnancy or skin transplantation. However， whereas there was no impact on second pregnancy as a result of the persistence of fetal-primed memory CD8 T cells in the mother， skin grafts bearing the same antigen were rejected more rapidly. Altogether， our data suggest that fetal antigen exposure during pregnancy induces the differentiation of long-lived maternal CD8 T cells with context-dependent， selective effector dysfunction. This programmed effector dysfunction provides temporal and systemic restraint of maternal anti-fetal alloreactivity to promote reproductive fitness efficiently， while preserving potentially protective effector T cell responses.
