Inhibition of murine gammadelta lymphocyte expansion and effector function by regulatory alphabeta T cells is cell-contact-dependent and sensitive to GITR modulation

Eur J Immunol. 2010 Jan;40(1):61-70. doi: 10.1002/eji.200939715.


Gammadelta T cells are highly cytolytic lymphocytes that produce large amounts of pro-inflammatory cytokines during immune responses to multiple pathogens. Furthermore, their ability to kill tumor cells has fueled the development of gammadelta-T-cell-based cancer therapies. Thus, the regulation of gammadelta-T-cell activity is of great biological and clinical relevance. Here, we show that murine CD4+CD25+ alphabeta T cells, the vast majority of which express the Treg marker, Foxp3, abolish key effector functions of gammadelta T cells, namely the production of the pro-inflammatory cytokines, IFN-gamma and IL-17, cytotoxicity, and lymphocyte proliferation in vitro and in vivo. We further show that suppression is dependent on cellular contact between Treg and gammadelta T cells, results in the induction of an anergic state in gammadelta lymphocytes, and can be partially reversed by manipulating glucocorticoid-induced TNF receptor-related protein (GITR) signals. Our data collectively dissect a novel mechanism by which the expansion and pro-inflammatory functions of gammadelta T cells are regulated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Communication*
  • Cell Proliferation
  • Coculture Techniques
  • Cytokines / biosynthesis
  • Cytokines / immunology
  • Glucocorticoid-Induced TNFR-Related Protein
  • Mice
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell, alpha-beta / deficiency
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • Receptors, Nerve Growth Factor / immunology*
  • Receptors, Tumor Necrosis Factor / immunology*
  • T-Lymphocyte Subsets / cytology*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Regulatory / immunology*


  • Cytokines
  • Glucocorticoid-Induced TNFR-Related Protein
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, Nerve Growth Factor
  • Receptors, Tumor Necrosis Factor
  • Tnfrsf18 protein, mouse