Differential requirements of naive and memory T cells for CD28 costimulation in autoimmune pathogenesis

Experimental autoimmune encephalomyelitis (EAE) is the most extensively stu died animal model of the human disease multiple sclerosis (MS). In EAE, CNS demyelination is induced by immunization with myelin proteins or adoptive transfer of myelin-reactive CD4(+) T cells. Since the antigen specificity o f the immune response believed to be responsible for the pathology of MS is not well defined, therapies that target aspects of T cell activation that are not antigen specific may be more applicable to the treatment of MS. As a result, understanding the role of costimulatory molecules in the activati on of naive and memory T cells has become an area of extensive investigatio n. Naive T cells require two signals for activation. Signal one is provided by engagement of the T cell receptor (TCR) with MHC/peptide complexes and provides antigen specificity to the immune response. The second signal, ter med costimulation, is usually provided by B7 molecules on APC to CD28 molec ules expressed on T cells and is antigen-independent. This review will disc uss our current understanding of costimulation in the induction and perpetu ation of EAE, as well as the potential of costimulaton blockade in the trea tment of MS.