IFN-γ-producing and IL-17-producing γδ T cells differentiate at distinct developmental stages in murine fetal thymus

J Immunol. 2014 Mar 1;192(5):2210-8. doi: 10.4049/jimmunol.1302145. Epub 2014 Jan 31.

Abstract

γδ T cells develop at the double-negative (DN) 2 and DN3 stages and acquire functions to produce IL-17 and IFN-γ in fetal thymus. However, the relationship between differentiation stages and their functions was unclear. In this study, we found that, although IFN-γ-producing and IL-17-producing γδ T cells developed from DN2 cells, only IFN-γ-producing γδ T cells developed from DN3 cells, indicating the direct generation of IL-17-producing γδ T cells from the DN2 stage, not through the DN3 stage. Single-cell analysis revealed that DN2 cells contained heterogeneous γδ T cell precursors with or without an ability to develop IL-17 producers. Inactivation of B cell leukemia/lymphoma 11b, a zinc finger transcription factor responsible for transition from early to late stages of DN2 cells, completely abrogated the development of IL-17-producing γδ T cells, although a unique subset of IFN-γ-producing γδ T cells expressing a high level of promyelocytic leukemia zinc finger was able to develop. Thus, our results reveal that γδ T cells are functionally differentiated to IFN-γ and IL-17 producers at different developmental stages in fetal thymus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology*
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology*
  • Mice
  • Mice, Mutant Strains
  • Receptors, Antigen, T-Cell, gamma-delta / genetics
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • Repressor Proteins / genetics
  • Repressor Proteins / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • Thymus Gland / embryology*
  • Thymus Gland / immunology
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / immunology

Substances

  • Bcl11b protein, mouse
  • Interleukin-17
  • Receptors, Antigen, T-Cell, gamma-delta
  • Repressor Proteins
  • Tumor Suppressor Proteins
  • Interferon-gamma