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

Nat Immunol. 2012 Apr 1;13(5):511-8. doi: 10.1038/ni.2247.

Abstract

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 γ-chain 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Age Factors
  • Animals
  • CD24 Antigen / immunology
  • CD24 Antigen / metabolism
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology*
  • Cell Lineage / immunology
  • Fetus / cytology
  • Fetus / immunology
  • Flow Cytometry
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Interleukin-17 / immunology
  • Interleukin-17 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Models, Immunological
  • Mycobacterium tuberculosis / immunology
  • Mycobacterium tuberculosis / metabolism
  • Principal Component Analysis
  • Receptors, Antigen, T-Cell, gamma-delta / classification
  • Receptors, Antigen, T-Cell, gamma-delta / genetics*
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • Thymus Gland / cytology
  • Thymus Gland / immunology*
  • Thymus Gland / metabolism
  • Transcription Factors / immunology
  • Transcription Factors / metabolism
  • Transcriptome / genetics
  • Transcriptome / immunology*

Substances

  • CD24 Antigen
  • Cd24a protein, mouse
  • Interleukin-17
  • Receptors, Antigen, T-Cell, gamma-delta
  • Transcription Factors
  • Interferon-gamma

Associated data

  • GEO/GSE15907