PREVENTION AND TREATMENT OF RELAPSING AUTOIMMUNE ENCEPHALOMYELITIS WITH MYELIN PEPTIDE-COUPLED SPLENOCYTES

Injection of antigen cross-linked accessory cells has proven to be an efficient and highly selective approach for inducing epitope-specific peripheral tolerance, This approach has been used successfully to inhi bit induction of experimental autoimmune encephalomyelitis (EAE) and t o dissect the relative dominance of component encephalitogenic determi nants that contribute to both acute and relapsing EAE, In this study, we evaluated the tolerogenic effect of the dominant encephalitogenic e pitope for SJL/J mice, residues 139-151 of myelin proteolipid proteins (PLP), on the induction and relapses of EAE induced actively with PLP 139-151/CFA, Our results demonstrate the powerful protective effect of treating mice before induction of EAE with PLP139-151-conjugated sple nocytes (SPL) on the incidence and severity of both the initial episod e and the first relapse of EAE. Moreover, treatment of mice on the fir st day of onset of clinical signs of EAE reduced the severity of the f irst relapse, apparently by reducing T cell recognition of PLP139-151, although no significant therapeutic effect was observed during the in itial treated clinical episode, These data demonstrate the utility of using neuroantigen-coupled accessory cells to prevent and treat relaps ing EAE. (C) 1996 Wiley-Liss, Inc.