NASAL ADMINISTRATION OF MULTIPLE ANTIGENS SUPPRESSES EXPERIMENTAL AUTOIMMUNE MYASTHENIA-GRAVIS, ENCEPHALOMYELITIS AND NEURITIS

Oral tolerization with acetylcholine receptor (AChR) and myelin basic protein (MBP) prior to immunization with AChR+MBP+complete Freund's ad juvant (CFA) alleviated clinical signs of experimental autoimmune myas thenia gravis (EAMG)+experimental allergic encephalomyelitis (EAE) and AChR- or MBP-specific T and B cell responses. Tolerance induced via t he nasal route needs much less tolerogen and may still be as effective as oral tolerance induction. We now immunized Lewis rats with AChR+MB P+bovine peripheral nerve myelin (BPM)+CFA, which resulted in a multip hasic clinical picture with a combination of clinical signs of the EAM G+EAE+experimental allergic neuritis (EAN), accompanied by massive mac rophage infiltrations in sections of muscle, spinal cord and sciatic n erve, and strong T and B cell responses to AChR, MBP and BPM in lympho id organs. Nasal administration of mu g doses of AChR+MBP+BPM prior to immunization with a mixture of these antigens+CFA effectively suppres sed the incidence and severity of clinical disease, reduced macrophage infiltrations in sections of muscle, spinal cord and sciatic nerve, a nd down-regulated autoreactive T cell responses to the three antigens in lymphoid organs. Numbers of AChR-, MBP-, BPM-reactive Th1 type of c ytokine interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha mRNA expression in lymph node cells were markedly suppressed, while transf orming growth factor-beta (TGF-beta) mRNA expression was upregulated f rom nasally tolerized rats, suggesting an active suppression mechanism may act partly in the induction of tolerance. The results implicate t he possibility to establish multiple autoantigen-based vaccination for the prevention of autoimmune diseases in humans. (C) 1998 Elsevier Sc ience B.V.