Induction of low dose oral tolerance in IL-10 deficient mice with experimental autoimmune encephalomyelitis.
IL-10 has been shown to be an important anti-inflammatory mediator that has both down-regulatory and immunomodulatory effects. Utilizing IL-10(-/-) mice we demonstrate the induction of low dose oral tolerance characterized by the up-regulation of TGF-beta and IL-4 and the suppression of Ag specific proliferation with little suppression of INF-gamma. More severe EAE was found in IL-10(-/-) mice than in wild type controls, however, feeding resulted in amelioration of disease severity in both groups. Orally tolerized IL-10(-/-) mice had greater disease severity compared to orally tolerized wild type mice. IL-4 was present in the GALT of IL-10(-/-) mice and up-regulation of TGF-beta was detected in the lamina propria of fed mice. These results demonstrate that IL-10 is not required for the induction of low dose oral tolerance but is required for the regulation of INF-gamma which affects severity of disease in tolerized mice.
Gonnella
Patricia A
PA
Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. patricia.gonnella@childrens.harvard.edu
Waldner
Hans Peter
HP
Kodali
Dhatri
D
Weiner
Howard L
HL
D000284:Administration, Oral; D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D017353:Gene Deletion; D006023:Glycoproteins / Q000008:administration & dosage* / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology*; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000378:metabolism
D006023:Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D016212:Transforming Growth Factor beta; C445081:myelin oligodendrocyte glycoprotein (35-55); D016753:Interleukin-10