Pregnancy promotes tolerance to future offspring by programming selective dysfunction in long-lived maternal T cells

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

Wherry, E. John¹  Porrett, Paige M.²  Xu, Rong³ 

[1] and;Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA;Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

关键词: alloimmunization;    transplantation;    exhaustion;    PD‐;    1;    fetomaternal;   

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

CC BY