Innate γδ T cells function in the early phase of immune responses. Although innate γδ 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, γδ 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 γδ effector cells. A high-resolution transcriptome analysis of all emergent γδ thymocyte subsets segregated on the basis of use of the TCR γchain or δ-chain indicated the existence of three separate subtypes of γδ effector cells in the thymus. The immature γδ subsets were distinguished by unique transcription-factor modules that program effector function.
Bibliographical noteFunding Information:
We thank M. Mohrs (Trudeau Institute) for IL-4–GFP reporter mice; H. Birchmeier (Max-Delbrück-Center for Molecular Medicine Berlin) for Axin2 reporter mice; V. Lefebvre (Cleveland Clinic) for Sox5 reporter mice; K. Rock (University of Massachusetts Medical School) for Ctsl−/− mice; E. Huseby (University of Massachusetts Medical School) for Cd74−/− mice; S. Davis (Harvard Medical School) for the ConsolidateProbeSets module and PopulationDistances PCA program; A. Hayday (King’s College, London) for anti-Vδ1 (17D1); members of the ImmGen Consortium for discussions; the ImmGen core team (M. Painter, J. Ericson and S. Davis) for help with data generation and processing; and eBioscience, Affymetrix and Expression Analysis for support of the ImmGen Project. Core resources supported by the Diabetes Endocrinology Research Center (DK32520) were used. Supported by the National Institute of Allergy and Infectious Diseases of the US National Institutes of Health (R24 AI072073 to the ImmGen group, and CA100382 to J.K.).