A temporal differentiation program after birth delineates γδ T cell immunity

Abstract

Type 1 and type 3 γδ T cells develop in the embryonic thymus, yet it is not known whether they continue to differentiate after birth in tissues. Here, we show that in the first week of life, intestinal γδ T cells up-regulated many T cell activation and type 3 genes, while the postweaning period was dominated by induction of genes related to effector function, type 1 immunity, and cytotoxicity. During this period, γδ T cells protected the gut from fungal infection. In the adult intestine, type 3 interleukin-17–producing γδ T cells (γδT17 cells) had a distinct phenotype, a Tbet-dependent type 1 immune profile and enhanced T cell receptor (TCR) signaling. Last, we found a γδT17 cell–like population in the neonatal human gut. Collectively, our data suggest that γδ T cells continue to mature after they leave the thymus and, upon localization to the gut, a dynamic temporal differentiation program reshapes type 3 cells into Tbet + type 1 effectors with heightened TCR activity.