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- W85962927 abstract "Experimental autoimmune neuritis (EAN) in Lewis rats serves as an animal model of human inflammatory demyelinating neuropathies. We previously demonstrated that EAN actively induced by immunization with bovine PNS-myelin can be suppressed by feeding of myelin. This myelin-specific oral tolerance (OT) was enhanced by coapplication of cholera toxin (CT).In the present study, EAN induced by immunization with a neuritogenic P2 peptide was completely prevented by precedent feeding of the peptide. Oral application of the P2 peptide mediated tolerance as efficient as did nasal administration. In contrast to OT by myelin, addition of CT completely prevented oral induction of tolerance to peptide-induced EAN, while adjuvant feeding alone did not modulate disease. As a possible immunological basis to explain the prevention of OT induction by CT, we identified a highly enhanced protein-specific in vitro proliferation of splenocytes from antigen/CT-fed animals compared to those of rats fed with the antigen only. The opposite effects of oral CT in combination with proteins versus myelin confirm our former assumption that CT augments myelin-induced tolerance by its binding to gangliosides present in the myelin but not in the P2 peptide solution, while free CT prevents the induction of OT. It is suggested that CT is a useful adjuvant for OT if coadministered with myelin, but requires chemical linkage to proteins to exert this function. Regulatory lymphocytes orally induced by feeding the protein keyhole limpet hemocyanine (KLH) slightly ameliorated peptide-induced EAN via bystander mechanisms, but injection of KLH in close proximity to the site of peptide-immunization was essential. The restriction of bystander suppression to that site in the lymphoid system where neuritogenic T cells are activated may limit the impact of OT as a bonafide treatment strategy in human autoimmune diseases and underscores the necessity to identify the autoantigens involved." @default.
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- W85962927 date "2001-05-01" @default.
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- W85962927 title "Oral tolerance in experimental autoimmune neuritis (EAN) of the Lewis rat" @default.
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- W85962927 doi "https://doi.org/10.1016/s0165-5728(01)00276-4" @default.
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