The role of B7 costimulation in the development of experimental autoimmune encephalomyelitis.

摘要

T cells require two signals for full activation. The first is the antigen specific T cell receptor-MHC/peptide interaction. The second is an antigen non-specific “costimulatory signal” provided by the antigen presenting cell. The B7-CD28/CTLA-4 pathway, as a major costimulatory pathway for T cells, has been implicated in the regulation of peripheral tolerance and in the development of autoimmune diseases. In this study, we examined the role of B7 costimulation in experimental autoimmune encephalomyelitis (EAE). EAE is an inflammatory demyelinating disease of the central nervous system, induced in genetically susceptible animals by immunization with myelin antigens or transfer of myelin-specific T cells. We dissected the involvement of B7-1 and B7-2 in various stages of EAE development and found it to be critical in both the induction and effector phases of myelin oligodendrocyte glycoprotein (MOG)-induced EAE in C57BL/6 mice. During the induction phase, B7 interactions were required for the expansion of autoreactive T cells and regulated T cell differentiation. B7 costimulation during the effector phase was important for T cells to infiltrate the CNS parenchyma and mediate tissue damage. However, the requirements for B7-1 and B7-2 in EAE pathogenesis were distinct between different genetic backgrounds of mice. This observation encouraged us to search for additional B7-like molecules and led to the identification and characterization of a novel member of the B7 family of costimulatory molecules.