Induction of IL-10-producing CD4(+)CD25(+ )T cells in animal model of collagen-induced arthritis by oral administration of type II collagen

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 IgG(1 )and decreased serum IgG(2a )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-β from mononuclear lymphocytes was increased in the tolerized animals, and CD4(+ )T cells isolated from tolerized mice did not respond with induction of IFN-γ 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

Comparisons of IL-10 and transforming growth factor (TGF)-β production by mononuclear lymphocytes from lymphoid organs of tolerized and nontolerized mice

<p><b>Copyright information:</b></p><p>Taken from "Induction of IL-10-producing CD4CD25T cells in animal model of collagen-induced arthritis by oral administration of type II collagen"</p><p>Arthritis Research & Therapy 2004;6(3):R213-R219.</p><p>Published online 11 Mar 2004</p><p>PMCID:PMC416445.</p><p>Copyright © 2004 Min et al., licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.</p> Organs were extracted from normal DBA/1, and tolerized and nontolerized collagen-induced arthritis (CIA) mice at 5 weeks after primary immunization with type II collagen (CII) for induction of CIA. Mononuclear cells were isolated from the Peyer's patch and the spleen, and production of IL-10 and TGF-β was assessed by sandwich ELISA analyses of culture supernatants. The data represent average values from three independent measurements