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.