AN INVESTIGATION OF CD137 AND CD137 LIGAND ACTIVITIES ON MURINE MICROGLIA

Abstract

CD137 (4-1BB, TNFRSF9) from the tumor necrosis factor (TNF) receptor family is a potent T cell co-stimulatory molecule expressed on activated T cells. CD137 ligand (CD137L) is expressed on antigen presenting cells (APC) including murine microglia. Stimulated by CD137, CD137L signaling activates microglia cell lines and primary microglia cells in vitro leading to morphological changes, enhanced adhesion, increase in secretion of pro-inflammatory cytokines and soluble mediators, elevated reactive oxygen species (ROS) production and increase in phagocytosis. CD137L-activated microglia induce apoptosis in oligodendrocytes, the myelin producers in the CNS, and this cell death is found to be CD137L-dependent and mediated by ROS. CD137L is important for microglia activation in vivo, as CD137L-/- mice result in lower microglia activation and fewer oligodendrocytes' apoptosis during Experimental Autoimmune Encephalomyelitis (EAE), which may be due to fewer infiltrating T cells and less profound inflammation. Further clinical implications or relevance may arise from the murine findings.