Induction of oral tolerization in CD86 deficient mice: a role for CD86 and B cells in the up-regulation of TGF-beta.
Feeding myelin oligodendrocyte glycoprotein (MOG) followed by immunization results in induction of oral tolerance evidenced by the amelioration of experimental autoimmune encephalomyelitis (EAE). Oral tolerization is characterized by the suppression of Th1 responses and up-regulation of Th2 responses and TGF-beta. To identify the costimulatory molecules and cell types involved in cytokine-mediated suppression we examined wild type mice and mice deficient for either CD86 (CD86-/-) or B cells (muMT). Oral tolerance was found in CD86-/- mice evidenced by amelioration of disease severity, decreased proliferative responses and IFN-gamma production and increased IL-4. TGF-beta was not up-regulated in CD86-/- or muMT mice but was increased in wild type mice. Analysis of the gut associated lymphoid tissue (GALT) of different mouse strains (C57BL/6 and PLJxSJL F1) fed distinct myelin antigens (MOG and myelin basic protein, MBP) showed that TGF-beta was increased in wild type mice of both strains by 3 days post-immunization and further increased with time. In contrast, no up-regulation of TGF-beta was found in the GALT of CD86-/- or muMT mice. These results demonstrate that CD86 is not required for oral tolerization and that both CD86 and B cells are important for the up-regulation of TGF-beta following oral antigen.
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@tch.harvard.edu
Chen
Youhai H
YH
Waldner
Hanspeter
H
Weiner
Howard L
HL
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D051940:B7-2 Antigen / Q000235:genetics / Q000502:physiology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D007108:Immune Tolerance / Q000235:genetics / Q000276:immunology; D007422:Intestines / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D009055:Mouth / Q000276:immunology; D010581:Peyer's Patches / Q000737:chemistry / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000378:metabolism*; D015854:Up-Regulation
D051940:B7-2 Antigen; D016212:Transforming Growth Factor beta