Oral tolerance in EAE: reversal of tolerance by T helper cell cytokines.
Oral administration of myelin basic protein (MBP) inhibits clinical and histopathological manifestations of experimental autoimmune encephalomyelitis (EAE), but only partially reduces serum anti-MBP antibody titers. We report here that orally administered MBP alters the isotypic distribution of anti-MBP antibody-forming cells (AFC) among various lymphoid tissues, with the most profound differences seen in mucosal tissues. We observed an isotype-selective reduction in anti-MBP IgA but not IgM AFC frequencies in Peyer's patches. The anti-MBP IgA AFC frequencies could be reconstituted by addition of interleukin 4 (IL-4) and interleukin 5(IL-5). The cytokines did not appear to generate de novo responses since no increases in anti-MBP lgA AFC frequencies were observed in control cultures. These results indicate that decreased antibody production, as a result of oral antigen administration, can be reversed by exposure to the appropriate cytokines.
Kelly
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Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock 72205, USA. kkelly@biomed.uams.edu
Whitacre
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D000284:Administration, Oral; D000818:Animals; D000921:Antibody-Producing Cells / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000494:pharmacology / Q000502:physiology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D007108:Immune Tolerance / Q000187:drug effects* / Q000502:physiology*; D007070:Immunoglobulin A / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D007700:Kinetics; D007958:Leukocyte Count / Q000187:drug effects; D008221:Lymphoid Tissue / Q000276:immunology / Q000473:pathology; D008297:Male; D004676:Myelin Basic Protein / Q000008:administration & dosage* / Q000276:immunology / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism*
D016207:Cytokines; D007070:Immunoglobulin A; D007075:Immunoglobulin M; D004676:Myelin Basic Protein