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

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.