Costimulation of memory T-cells by ICOS: A potential therapeutic target for autoimmunity?

Approaches that target costimulatory receptors are independent of T-cell re ceptor specificity and may be useful for T-cell-mediated diseases in which the antigens involved are not well defined. However, the proper costimulato ry pathways need to be targeted. For example, therapies for human T-cell-me diated diseases need to be effective against previously activated memory ce lls. In this review, we use autoimmune demyelination as a paradigm for esta blished immune-mediated pathogenesis. Studies with the human disease multip le sclerosis and the rodent model experimental autoimmune encephalomyelitis have suggested that the effectiveness of CD28 blockade, as a therapeutic s trategy for established autoimmune demyelination, may be limited. ICOS, a r eceptor that appears to be involved in the costimulation of previously acti vated T-cells, may be an attractive alternative. (C) 2001 Academic Press.