Regulatory T cells: Master regulators for the success of pregnancy

Regulatory T cells (Treg cells) are an immunosuppressive subset of helper T cells, which are crucial to maintaining immune homeostasis, self-tolerance, and feto-maternal tolerance. Fetal alloantigens are recognized by conventional T cells; however, Treg cells, directly and indirectly, suppress their cytotoxic activities against fetuses. Murine models show that paternal antigen-specific Treg cells (PA-Treg cells) expand at the feto-maternal interface during pregnancies and seminal plasma-priming is important to this process. In humans, extensive epidemiological data of preeclampsia suggest that insufficient PA-specific tolerance relates to its development, but some epidemiological studies suggest the relationship between PA-specific tolerance and miscarriages. Recent basic research studies imply the immunological differences between miscarriages and preeclampsia from the standpoint of PA-Treg cells, which support epidemiological evidence. In this section, we review the latest understanding of Treg cell-mediated tolerance and prospects of clinical applications of immunological therapies and preventions for miscarriages and preeclampsia.