Identification of a novel activation-inducible protein of the tumor necrosis factor receptor superfamily and its ligand

Among members of the tumor necrosis factor receptor (TNFR) superfamily, 4-1 BB, CD27, and glucocorticoid-induced tumor necrosis factor receptor family- related gene (GITR) share a striking homology in the cytoplasmic domain. He re we report the identification of a new member, activation-inducible TNFR family member (AITR), which belongs to this subfamily, and its ligand. The receptor is expressed in lymph node and peripheral blood leukocytes, and it s expression is up-regulated in human peripheral mononuclear cells mainly a fter stimulation with anti-CD3/CD28 monoclonal antibodies or phorbol 12-myr istate 13-acetate/ionomycin. AITR associates with TRAF1 (TNF receptor-assoc iated factor 1), TRAF2, and TRAF3, and induces nuclear factor (NF)-kappa B activation via TRAF2. The ligand for AITR (AITRL) was found to be an undesc ribed member of the TNF family, which is expressed in endothelial cells. Th us, AITR and AITRL seem to be important for interactions between activated T lymphocytes and endothelial cells.