title: Nasal administration of multiple antigens suppresses experimental autoimmune myasthenia gravis, encephalomyelitis and neuritis.
abstract: Oral tolerization with acetylcholine receptor (AChR) and myelin basic protein (MBP) prior to immunization with AChR+MBP+ complete Freund's adjuvant (CFA) alleviated clinical signs of experimental autoimmune myasthenia gravis (EAMG)+experimental allergic encephalomyelitis (EAE) and AChR- or MBP-specific T and B cell responses. Tolerance induced via the nasal route needs much less tolerogen and may still be as effective as oral tolerance induction. We now immunized Lewis rats with AChR+MBP+bovine peripheral nerve myelin (BPM)+CFA, which resulted in a multiphasic clinical picture with a combination of clinical signs of the EAMG+EAE+experimental allergic neuritis (EAN), accompanied by massive macrophage infiltrations in sections of muscle, spinal cord and sciatic nerve, and strong T and B cell responses to AChR, MBP and BPM in lymphoid organs. Nasal administration of microg doses of AChR+MBP+BPM prior to immunization with a mixture of these antigens+CFA effectively suppressed the incidence and severity of clinical disease, reduced macrophage infiltrations in sections of muscle, spinal cord and sciatic nerve, and down-regulated autoreactive T cell responses to the three antigens in lymphoid organs. Numbers of AChR-, MBP-, BPM-reactive Th1 type of cytokine interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha mRNA expression in lymph node cells were markedly suppressed, while transforming growth factor-beta (TGF-beta) mRNA expression was upregulated from nasally tolerized rats, suggesting an active suppression mechanism may act partly in the induction of tolerance. The results implicate the possibility to establish multiple autoantigen-based vaccination for the prevention of autoimmune diseases in humans.
authors.affiliation: Division of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
authors.forename: F D
authors.initials: FD
authors.lastname: Shi
authors.forename: X F
authors.initials: XF
authors.lastname: Bai
authors.forename: B G
authors.initials: BG
authors.lastname: Xiao
authors.forename: P H
authors.initials: PH
authors.lastname: van der Meide
authors.forename: H
authors.initials: H
authors.lastname: Link
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001324:Autoantigens / Q000008:administration & dosage* / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology / Q000517:prevention & control*; D002417:Cattle; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D000939:Epitopes / Q000235:genetics; D005260:Female; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000096:biosynthesis; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D018908:Muscle Weakness / Q000276:immunology / Q000378:metabolism; D009157:Myasthenia Gravis / Q000378:metabolism / Q000517:prevention & control; D004676:Myelin Basic Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000276:immunology; D009444:Neuritis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew; D011950:Receptors, Cholinergic / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D001324:Autoantigens; D000939:Epitopes; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D004676:Myelin Basic Protein; D012333:RNA, Messenger; D011950:Receptors, Cholinergic; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma