TREATMENT WITH INTACT ANTI-B7-1 MAB DURING DISEASE REMISSION ENHANCESEPITOPE SPREADING AND EXACERBATES RELAPSES IN R-EAE

PLP139-151-induced experimental autoimmune encephalomyelitis in the SJ L mouse is a Th1-mediated inflammatory demyelinating disease character ized by a relapsing-remitting clinical course (R-EAE). Clinical relaps es are mediated by T cells specific for a non-cross reactive secondary PLP epitope (PLP178-191) induced by epitope spreading. We have previo usly shown that B7-1 expression is upregulated in SJL mice undergoing R-EAE and in vivo treatment during remission with F(ab) fragments of a nti-B7-1 mAb, blocked epitope spreading and disease progression. In co ntrast, the present study shows that treatment with intact anti-B7-1 m Ab exacerbated clinical disease relapses and enhanced CNS demyelinatio n. Anti-B7-1-treated mice showed enhanced in vivo delayed-type hyperse nsitivity (DTH) to the relapse-associated PLP178-191 epitope and respo nses to the immunodominant MBP84-104 epitope which are absent in the c ontrols. Thus, ligation of B7-1 by intact mAbs has effects opposite to those of anti-B7-1 F(ab) fragments suggesting that the mAb is directl y signaling through B7-1 expressed on T cells and/or APCs. (C) 1997 El sevier Science B.V.