TNFRSF18 or GITR (glucocorticoid-induced TNF receptor family-regulated gene) is a 25 kD TNF receptor superfamily member (also known as AITR and TNFRSF18) originally identified in the mouse by comparing untreated and dexamethasone-treated murine T cell hybridoma cells. Human GITR was subsequently identified by searching an expressed sequence tag database. GITR is expressed on activated lymphocytes and is upregulated by T cell receptor engagement. The cytoplasmic domain of GITR is homologous to CD40, 4-1BB and CD27 and has been shown to interact with TRAF 1-3, but not TRAF 5 or 6. GITR signaling has been shown to regulate T cell proliferation and TCR-mediated apoptosis, and to break immunological self-tolerance. GITR appears to be highly expressed on CD4+CD25+ T regulatory cells and has been shown to induce NF-kB activation through TRAF2/NIK signaling. GITR has been proposed to be involved in the development of regulatory T cells and to regulate the activity of Th1 subsets. GITR binds GITRL, a TNF superfamily ligand expressed on endothelial cells, dendritic cells, macrophages, and B cells.