The GITR-GITRL interaction: co-stimulation or contrasuppression of regulatory activity?

Nat Rev Immunol. 2006 Aug;6(8):613-8. doi: 10.1038/nri1867.


Stimulation of T cells through GITR (glucocorticoid-induced tumour-necrosis-factor-receptor-related protein) has been shown to enhance immunity to tumours and viral pathogens, and to exacerbate autoimmune disease. The effects of stimulation through GITR are generally thought to be caused by attenuation of the effector activity of immunosuppressive CD4+ CD25+ regulatory T (T(Reg)) cells. Here we propose a model in which GITR-GITR-ligand interactions co-stimulate both responder T-cell functions and the suppressive functions of T(Reg) cells.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / immunology
  • Glucocorticoid-Induced TNFR-Related Protein
  • Humans
  • Lymphocyte Activation / immunology
  • Mice
  • Models, Immunological
  • Neoplasms / immunology
  • Protein Binding / immunology
  • Receptors, Nerve Growth Factor / immunology
  • Receptors, Nerve Growth Factor / metabolism*
  • Receptors, Tumor Necrosis Factor / immunology
  • Receptors, Tumor Necrosis Factor / metabolism*
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology*
  • Tumor Necrosis Factors / immunology
  • Tumor Necrosis Factors / metabolism*


  • Glucocorticoid-Induced TNFR-Related Protein
  • Receptors, Nerve Growth Factor
  • Receptors, Tumor Necrosis Factor
  • TNFRSF18 protein, human
  • TNFSF18 protein, human
  • Tnfrsf18 protein, mouse
  • Tnfsf18 protein, mouse
  • Tumor Necrosis Factors