Cloning and characterization of GITR ligand

The gene encoding the natural ligand of murine glucocorticoid-induced tumor necrosis factor receptor ( GITR) was cloned and characterized. The putative GITR ligand (GITRL) is composed of 173 amino acids with features resembling those of type II membrane proteins and is 51% identical to the human activation-inducible TNF receptor (AITR) ligand, TL6. Expression of the GITRL is restricted to immature and mature splenic dendritic cells. GITRL binds GITR expressed on HEK 293 cells and triggers NF-kappaB activation. Functional studies reveal that soluble CD8-GITRL prevents CD4(+)CD25(+) regulatory T-cell-mediated suppressive activities.