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

How GITR (glucocorticoid-induced tumour-necrosis-factor-receptor-related protein) regulates an immune response is not clearly understood. This article proposes a model in which the interaction of GITR with its ligand co-stimulates the respective functions of both responder T cells and CD4 + CD25 + regulatory T cells. 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.