B7-MEDIATED COSTIMULATION CAN EITHER PROVOKE OR PREVENT CLINICAL MANIFESTATIONS OF EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS

T-cell activation requires signalling provided by ligation of the T-ce ll receptor for antigen (TCR) and a second antigen (Ag) nonspecific si gnal, known as costimulation. The B7 receptors, CD80 (B7-1) and CD86 ( B7-2), on the Ag-presenting cell (APC), interact with T-cell CD28 or C TLA-4 to deliver a costimulatory signal, which is particularly importa nt for Th1 activation. Experimental allergic encephalomyelitis (EAE) i s an autoimmune disorder, induced by Th1 cells directed against myelin antigens that provides an in vivo model for studying the role of B7-m ediated costimulation in the induction of a pathological immune respon se. Using a soluble fusion protein ligand for the B7 receptors, as wel l as specific monoclonal antibodies specific for either CD80 or CD86, it has been demonstrated that B7 costimulation plays a prominent role in determining clinical disease outcome in EAE. Here we review recent data indicating that a paradoxical exacerbation of disease as well as the expected amelioration of disease can occur with costimulatory rece ptor blockade.