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

Ethan M Shevach; Geoffrey L Stephens

doi:10.1038/nri1867

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

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

Authors

Ethan M Shevach¹, Geoffrey L Stephens

Affiliation

¹ Cellular Immunology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. eshevach@niaid.nih.gov

PMID: 16868552
DOI: 10.1038/nri1867

Abstract

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*

Substances

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