Development of Experimental Autoimmune Encephalomyelitis Critically Depends on CD 137 Ligand Signaling.

Multiple sclerosis (MS) is a degenerative autoimmune disease of the CNS. Experimental autoimmune encephalomyelitis (EAE) is a commonly used murine model for MS. Here we report that CD137 ligand (CD137L, 4-1BB ligand, TNFS9), a member of the TNF super-family, is critical for the development of EAE. EAE symptoms were significantly ameliorated in CD137L^-/- mice. In the absence of CD137L, myelin oligodendrocyte glycoprotein (MOG)-specific T-cells secreted lower levels of T_hl/T_h17 cell-associated cytokines. MOG-specific T-cells also trafficked less efficiently to the CNS in CD 137L^-/- mice, possibly as a consequence of reduced expression of vascular cell adhesion molecule-1 (VCAM-1), which regulates leukocyte extravasation. Thus, CD137L regulates many functions of MOG-specific T-cells that contribute to EAE and may represent a novel therapeutic target for the treatment of MS. [ABSTRACT FROM AUTHOR]