The role of CTLA-4 in tolerance induction and T cell differentiation in experimental autoimmune encephalomyelitis: i.p. antigen administration

Recent evidence suggests that co-stimulation provided by B7 molecules throu gh CTLA-4 is important in establishing peripheral tolerance. In the present study, we examined the kinetics of tolerance induction and T cell differen tiation following i.p. administration of myelin basic protein (MBP) Ac1-11 in mice transgenic for a TCR V(beta)8.2 gene derived from an encephalitogen ic T cell clone specific for MBP Ac1-11. Examination of the lymph node cell response after antigen administration demonstrated a dependence on CTLA-4 for i.p, tolerance induction. Examination of splenocyte responses suggested that i.p, antigen administration induced a T(h)2 response, which was poten tiated by anti-CTLA-4 administration. interestingly, i.p, tolerance was abl e to inhibit the induction of experimental autoimmune encephalomyelitis and anti-CTLA-4 administration did not alter this phenotype, suggesting that C TLA-4 blockade did not block tolerance induction. Thus, T cell differentiat ion and the dependence on CTLA-4 for tolerance induction following i.p. ant igen administration differs between lymph node and spleen in a model of org an-specific autoimmunity.