Role of costimulatory pathways in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis.
Multiple sclerosis is an immune-mediated disorder of the central nervous system. T lymphocytes are thought to play a central role in the initiation and potentially in the propagation of this disease. Two signals are required for T-cell activation. The first signal consists of the interaction of the T-cell receptor with antigen presented by the MHC molecule on antigen-presenting cells. The second signal requires engagement of costimulatory receptors on T cells with their ligands on antigen-presenting cells. Several costimulatory pathways have been shown to play an important role in T-lymphocyte activation. Here we will review the current literature on the contribution of the B7-1/2-CD28/CTLA-4, inducible costimulatory molecule-B7h, programmed death pathway 1-programmed death pathway ligand 1/ligand 2, CD40-CD154, OX40-OX40 ligand, and CD137-CD137 ligand pathways to the pathogenesis of multiple sclerosis and their potential roles as therapeutic targets.
Chitnis
Tanuja
T
Brigham and Women's Hospital, Harvard Medical School, Boston, Mass 02115, USA.
Khoury
Samia J
SJ
D000818:Animals; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D009103:Multiple Sclerosis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology