Intrathymic programming of effector fates in three molecularly distinct γδ T cell subtypes

Innate gamma delta T cells function in the early phase of immune responses. Although innate gamma delta T cells have often been studied as one homogenous population, they can be functionally classified into effector subsets on the basis of the production of signature cytokines, analogous to adaptive helper T cell subsets. However, unlike the function of adaptive T cells, gamma delta effector T cell function correlates with genomically encoded T cell antigen receptor (TCR) chains, which suggests that clonal TCR selection is not the main determinant of the differentiation of gamma delta effector cells. A high-resolution transcriptome analysis of all emergent gamma delta thymocyte subsets segregated on the basis of use of the TCR gamma-chain or delta-chain indicated the existence of three separate subtypes of gamma delta effector cells in the thymus. The immature gamma delta subsets were distinguished by unique transcription-factor modules that program effector function.