Costimulatory signal blockade in murine relapsing experimental autoimmune encephalomyelitis

Blockade of the CD28-B7 or CD40L-CD40 T cell costimulatory signals prevents induction of experimental autoimmune encephalomyelitis (EAE). However, the effect of simultaneous blockade of these signals in EAE is unknown. We sho w that administration of either MR1 (to block CD40L) or CTLA4Ig (to block B 7) after immunization or after the first attack protects from EAE. Treatmen t with a combination of CTLA4Ig and MR1 provides additive protection, and i s associated with complete absence of mononuclear cell infiltrates in the c entral nervous system. and marked suppression of proliferation of primed T cells in the periphery. Selective B7-1 blockade did not protect from EAE. T hese observations have implications for therapy of autoimmune diseases, (C) 1999 Elsevier Science B.V. All rights reserved.