Thymic Selection Determines Gammadelta T Cell Effector Fate: Antigen-Naive Cells Make interleukin-17 and Antigen-Experienced Cells Make Interferon Gamma

Immunity. 2008 Jul 18;29(1):90-100. doi: 10.1016/j.immuni.2008.04.022. Epub 2008 Jun 26.

Abstract

gammadelta T cells uniquely contribute to host immune defense, but how this is accomplished remains unclear. Here, we analyzed the nonclassical major histocompatibility complex class I T10 and T22-specific gammadelta T cells in mice and found that encountering antigen in the thymus was neither required nor inhibitory for their development. But when triggered through the T cell receptor, ligand-naive lymphoid-gammadelta T cells produced IL-17, whereas ligand-experienced cells made IFN-gamma. Immediately after immunization, a large fraction of IL-17(+) gammadelta T cells were found in the draining lymph nodes days before the appearance of antigen-specific IL-17(+) *beta T cells. Thus, thymic selection determines the effector fate of gammadelta T cells rather than constrains their antigen specificities. The swift IL-17 response mounted by antigen-naive gammadelta T cells suggests a critical role for these cells at the onset of an acute inflammatory response to novel antigens.

Publication types

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

MeSH terms

  • Animals
  • Antigens / immunology
  • Antigens, Surface / immunology
  • Cell Differentiation / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Flow Cytometry
  • Histocompatibility Antigens Class I / immunology
  • Interferon-gamma / biosynthesis*
  • Interleukin-17 / biosynthesis*
  • Lymphocyte Activation / immunology*
  • Mice
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • T-Lymphocyte Subsets / cytology*
  • T-Lymphocyte Subsets / immunology
  • Thymus Gland / cytology
  • Thymus Gland / immunology

Substances

  • Antigens
  • Antigens, Surface
  • Histocompatibility Antigens Class I
  • Interleukin-17
  • Receptors, Antigen, T-Cell, gamma-delta
  • T10 antigen, mouse
  • T22 antigen
  • Interferon-gamma