Suppression of experimental autoimmune uveitis in rats by the oral administration of the uveitopathogenic S-antigen fragment or a cross-reactive homologous peptide.
The oral administration of S-antigen fragment (a synthetic peptide designated as peptide M and known to be uveitopathogenic for rat, guinea pig, and monkey) to Lewis rats prior to challenge with an emulsion of peptide M and CFA resulted in either a total or partial suppression of experimental autoimmune uveitis (EAU), a T cell-mediated autoimmune disease studied as a model for human uveitis and experimental autoimmune pinealitis (EPA). Both the clinical and histopathologic manifestations of the disease were suppressed in a dose-dependent manner. Pinealitis associated with EAU was also suppressed by the oral administration of peptide M. Additionally, ingestion of a fragment of baker's yeast (Saccharomyces cerevisiae) histone H3, which has five consecutive amino acids identical to peptide M and which has been found to be uveitopathogenic in Lewis rats, induced tolerance to either peptide M or synthetic histone H3 peptide. In addition, the proliferative response to peptide M was inhibited in peptide M-fed rats. The suppression of EAU and in vitro lymphocyte proliferative responses to peptide M were observed to be antigen specific, since oral feeding of a control protein (BSA) exerted no suppressive effect. Furthermore, the T cells isolated from the spleen and lymph nodes of animals rendered tolerant by oral administration of peptide M can transfer protection against EAU adoptively. These results demonstrate that the oral administration of an autoantigen or its homologous peptide initiates an antigen-specific cellular mechanism which may ameliorate EAU.
Singh
V K
VK
Molecular Biology Section, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892.
Kalra
H K
HK
Yamaki
K
K
Shinohara
T
T
D000284:Administration, Oral; D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D019393:Arrestin; D001327:Autoimmune Diseases / Q000276:immunology / Q000517:prevention & control*; D003429:Cross Reactions; D004306:Dose-Response Relationship, Immunologic; D005136:Eye Proteins / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D005260:Female; D006657:Histones / Q000276:immunology; D007108:Immune Tolerance; D007116:Immunization, Passive; D008213:Lymphocyte Activation; D010446:Peptide Fragments / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology; D014605:Uveitis / Q000276:immunology*
D000941:Antigens; D019393:Arrestin; D005136:Eye Proteins; D006657:Histones; D010446:Peptide Fragments