title: Induction of IL-10-producing CD4+CD25+ T cells in animal model of collagen-induced arthritis by oral administration of type II collagen.
abstract: Induction of oral tolerance has long been considered a promising approach to the treatment of chronic autoimmune diseases, including rheumatoid arthritis (RA). Oral administration of type II collagen (CII) has been proven to improve signs and symptoms in RA patients without troublesome toxicity. To investigate the mechanism of immune suppression mediated by orally administered antigen, we examined changes in serum IgG subtypes and T-cell proliferative responses to CII, and generation of IL-10-producing CD4+CD25+ T-cell subsets in an animal model of collagen-induced arthritis (CIA). We found that joint inflammation in CIA mice peaked at 5 weeks after primary immunization with CII, which was significantly less in mice tolerized by repeated oral feeding of CII before CIA induction. Mice that had been fed with CII also exhibited increased serum IgG1 and decreased serum IgG2a as compared with nontolerized CIA animals. The T-cell proliferative response to CII was suppressed in lymph nodes of tolerized mice also. Production of IL-10 and of transforming growth factor-beta from mononuclear lymphocytes was increased in the tolerized animals, and CD4+ T cells isolated from tolerized mice did not respond with induction of IFN-gamma when stimulated in vitro with CII. We also observed greater induction of IL-10-producing CD4+CD25+ subsets among CII-stimulated splenic T cells from tolerized mice. These data suggest that when these IL-10-producing CD4+CD25+ T cells encounter CII antigen in affected joints they become activated to exert an anti-inflammatory effect.
authors.affiliation: Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, Korea.
authors.forename: So-Youn
authors.initials: SY
authors.lastname: Min
authors.forename: Sue-Yun
authors.initials: SY
authors.lastname: Hwang
authors.forename: Kyung-Su
authors.initials: KS
authors.lastname: Park
authors.forename: Jae-Sun
authors.initials: JS
authors.lastname: Lee
authors.forename: Kang-Eun
authors.initials: KE
authors.lastname: Lee
authors.forename: Kyung-Wun
authors.initials: KW
authors.lastname: Kim
authors.forename: Young-Ok
authors.initials: YO
authors.lastname: Jung
authors.forename: Hyunk-Jae
authors.initials: HJ
authors.lastname: Koh
authors.forename: Ju-Ho
authors.initials: JH
authors.lastname: Do
authors.forename: Haerim
authors.initials: H
authors.lastname: Kim
authors.forename: Ho-Youn
authors.initials: HY
authors.lastname: Kim
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001169:Arthritis, Experimental / Q000097:blood / Q000139:chemically induced* / Q000473:pathology*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D024043:Collagen Type II / Q000276:immunology*; D005620:Freund's Adjuvant / Q000276:immunology; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis*; D008198:Lymph Nodes / Q000473:pathology; D008213:Lymphocyte Activation / Q000502:physiology; D051379:Mice; D008811:Mice, Inbred DBA; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D013154:Spleen / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
chemical_list: D024043:Collagen Type II; D007074:Immunoglobulin G; D015375:Receptors, Interleukin-2; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D007371:Interferon-gamma; D005620:Freund's Adjuvant