Costimulation of memory T-cells by ICOS: a potential therapeutic target for autoimmunity?
Approaches that target costimulatory receptors are independent of T-cell receptor specificity and may be useful for T-cell-mediated diseases in which the antigens involved are not well defined. However, the proper costimulatory pathways need to be targeted. For example, therapies for human T-cell-mediated diseases need to be effective against previously activated memory cells. In this review, we use autoimmune demyelination as a paradigm for established immune-mediated pathogenesis. Studies with the human disease multiple sclerosis and the rodent model experimental autoimmune encephalomyelitis have suggested that the effectiveness of CD28 blockade, as a therapeutic strategy for established autoimmune demyelination, may be limited. ICOS, a receptor that appears to be involved in the costimulation of previously activated T-cells, may be an attractive alternative.
Sporici
R A
RA
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Perrin
P J
PJ
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D015551:Autoimmunity; D018122:B7-1 Antigen / Q000502:physiology; D018106:CD28 Antigens / Q000502:physiology; D006801:Humans; D007156:Immunologic Memory; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D018122:B7-1 Antigen; D018106:CD28 Antigens; C556692:ICOS protein, human; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein