Publications

Abstract

Compared with lymphoid tissues, the immune cell compartment at mucosal sites is enriched with T cells bearing the gammadelta T-cell receptor (TCR). The female reproductive tract, along with the placenta and uterine decidua during pregnancy, are populated by gammadelta T cells predominantly expressing the invariant Vgamma6(+)Vdelta1(+) receptor. Surprisingly little is understood about the function of these cells. We found that the majority of gammadelta T cells in the non-pregnant uterus, pregnant uterus, decidua and placenta of mice express the transcription factor RORgammat and produce interleukin-17 (IL-17). In contrast, IFNgamma-producing gammadelta T cells were markedly reduced in gestational tissues compared with uterine-draining lymph nodes and spleen. Both uterine-resident invariant Vgamma6(+) and Vgamma4(+) gammadelta T cells which are more typically found in lymphoid tissues and circulating blood, were found to express IL-17. Vgamma4(+) gammadelta 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 gammadelta 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.