SUPPRESSION OF EXPERIMENTAL AUTOIMMUNE MYASTHENIA-GRAVIS AND EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS BY ORAL-ADMINISTRATION OF ACETYLCHOLINE-RECEPTOR AND MYELIN BASIC-PROTEIN - DOUBLE TOLERANCE

Oral administration of acetylcholine receptor (AChR) or myelin basic p rotein (MBP) to Lewis rat prior to immunization with AChR or MBP and c omplete Freund's adjuvant (CFA) has previously been shown to prevent o r delay the onset of experimental autoimmune myasthenia gravis (EAMG) or experimental allergic encephalomyelitis (EAE), which represent anim al models of myasthenia gravis and multiple sclerosis, respectively. H ere we show that Lewis rats immunized with AChR + MBP + CFA developed both signs of muscular weakness seen in EAMG and paresis characteristi c for EAE. This disease was associated with high levels of anti-AChR a nd anti-MBP antibody secreting cells and of AChR- and MBP-reactive INF -gamma secreting Th1-like cells in lymph nodes. The diseased rats also showed upregulation of AChR- and MBP-induced mRNA expression of IFN-g amma in lymph node cells. Oral tolerization with AChR and MBP in combi nation prior to immunization with AChR + MBP + CFA alleviated clinical disease as well as AChR- and MBP-specific B cell responses and autoan tigen-induced IFN-gamma secretion and production, but upregulated anti gen-induced TGF-beta mRNA expression in lymph node cells. The results implicate that oral tolerization simultaneously to more than one autoi mmune disease-related autoantigen is feasible, and that suppression of autoantigen-induced IFN-gamma and augmentation of TGF-beta are pivota l in tolerance induction.