The majority of murine γδ T cells at the maternal-fetal interface in pregnancy produce IL-17

Compared with lymphoid tissues, the immune cell compartment at mucosal sites is enriched with T cells bearing the gamma delta T-cell receptor (TCR). The female reproductive tract, along with the placenta and uterine decidua during pregnancy, are populated by gamma delta T cells predominantly expressing the invariant V gamma 6(+)V delta 1(+) receptor. Surprisingly little is understood about the function of these cells. We found that the majority of gamma delta T cells in the non-pregnant uterus, pregnant uterus, decidua and placenta of mice express the transcription factor ROR gamma t and produce interleukin-17 (IL-17). In contrast, IFN gamma-producing gamma delta T cells were markedly reduced in gestational tissues compared with uterine-draining lymph nodes and spleen. Both uterine-resident invariant V gamma 6(+) and V gamma 4(+) gamma delta T cells which are more typically found in lymphoid tissues and circulating blood, were found to express IL-17. V gamma 4(+) gamma delta T cells were particularly enriched in the placenta, suggesting a pregnancy-specific recruitment or expansion of these cells. A small increase in IL-17-producing gamma delta T cells was observed in allogeneic compared with syngeneic pregnancy, suggesting a contribution to regulating the maternal response to paternally-derived alloantigens. However, their high proportions also in non-pregnant uteri and gestational tissues of syngeneic pregnancy imply a role in the prevention of intrauterine infection or quality control of fetal development. These data suggest the need for a more rigorous evaluation of the role of IL-17 in sustaining normal pregnancy, particularly as emerging data points to a pathogenic role for IL-17 in pre-eclampsia, pre-term birth, miscarriage and maternal immune activation-induced behavioral abnormalities in offspring.