Three distinct developmental pathways for adaptive and two IFN-γ-producing γδ T subsets in adult thymus

Nat Commun. 2017 Dec 4;8(1):1911. doi: 10.1038/s41467-017-01963-w.

Abstract

Murine γδ T cells include subsets that are programmed for distinct effector functions during their development in the thymus. Under pathological conditions, different γδ T cell subsets can be protective or can exacerbate a disease. Here we show that CD117, CD200 and CD371, together with other markers, identify seven developmental stages of γδ T cells. These seven stages can be divided into three distinct developmental pathways that are enriched for different TCRδ repertoires and exhibit characteristic expression patterns associated with adaptive (γδTn), IFN-γ-producing (γδT1) and IFN-γ/IL-4-co-producing γδ T cells (γδNKT). Developmental progression towards both IFN-γ-producing subsets can be induced by TCR signalling, and each pathway results in thymic emigration at a different stage. Finally, we show that γδT1 cells are the predominating IFN-γ-producing subset developing in the adult thymus. Thus, this study maps out three distinct development pathways that result in the programming of γδTn, γδT1 and γδNKT cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / immunology
  • Cell Differentiation
  • Interferon-gamma / immunology
  • Interleukin-4 / immunology
  • Lymphopoiesis / immunology*
  • Mice
  • Natural Killer T-Cells / cytology
  • Natural Killer T-Cells / immunology
  • Proto-Oncogene Proteins c-kit / immunology
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • Signal Transduction
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • Thymocytes / cytology
  • Thymocytes / immunology*
  • Thymus Gland / cytology

Substances

  • Antigens, CD
  • Receptors, Antigen, T-Cell, gamma-delta
  • Interleukin-4
  • Interferon-gamma
  • Proto-Oncogene Proteins c-kit
  • antigens, CD200