TGF-beta-treated antigen presenting cells suppress collagen- induced arthritis through the promotion of Th2 responses.
Collagen-induced arthritis (CIA) is mediated by self-reactive CD4(+) T cells that produce inflammatory cytokines. TGF-beta(2)-treated tolerogenic antigen-presenting cells (Tol-APCs) are known to induce tolerance in various autoimmune diseases. In this study, we investigated whether collagen-specific Tol-APCs could induce suppression of CIA. We observed that Tol-APCs could suppress the development and severity of CIA and delay the onset of CIA. Treatment of Tol-APCs reduced the number of IFN-gamma- and IL-17-producing CD4(+) T cells and increased IL-4- and IL-5-producing CD4(+) T cells upon collagen antigen stimulation in vitro. The suppression of CIA conferred by Tol-APCs correlated with their ability to selectively induce IL-10 production. We also observed that treatment of Tol-APCs inhibited not only cellular immune responses but also humoral immune responses in the process of CIA. Our results suggest that in vitro-generated Tol-APCs have potential therapeutic value for the treatment of rheumatoid arthritis as well as other autoimmune diseases.
Jung
Sundo
S
School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea.
Park
Yoon-Kyung
YK
Lee
Hyunji
H
Shin
Jung Hoon
JH
Lee
Gap Ryol
GR
Park
Se-Ho
SH
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000276:immunology*; D001169:Arthritis, Experimental / Q000276:immunology*; D002645:Chickens; D024043:Collagen Type II / Q000276:immunology; D007108:Immune Tolerance / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology*; D053781:Transforming Growth Factor beta2 / Q000494:pharmacology*
D024043:Collagen Type II; D053781:Transforming Growth Factor beta2; D010047:Ovalbumin