Abstract
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.
Highlights
Collagen-induced arthritis (CIA) is an animal model for human rheumatoid arthritis (RA)
Th17 cells were identified by a profile of cytokines that is distinct from those observed in Th1 or Th2 subsets, and they could have a crucial role in chronic inflammatory or autoimmune diseases, such as colitis, asthma, experimental allergic encephalitis (EAE), and CIA (Nakae et al, 2003; Harrington et al, 2005; Langrish et al, 2005)
Ova-specific CD4+ T cells were isolated from immunized DO11.10 Tg mice and co-cultured with OVA-loaded tolerogenic antigen presenting cell (Tol-APC) or immunogenic antigen presenting cell (Imm-APC) for 72 h to evaluate T cell proliferation and IFN-γ production
Summary
Collagen-induced arthritis (CIA) is an animal model for human rheumatoid arthritis (RA). CIA can be induced by immunization with type II collagen (CII), the major protein constituent of articular cartilage (Courtenay et al, 1980). Th17 cells were identified by a profile of cytokines that is distinct from those observed in Th1 or Th2 subsets, and they could have a crucial role in chronic inflammatory or autoimmune diseases, such as colitis, asthma, experimental allergic encephalitis (EAE), and CIA (Nakae et al, 2003; Harrington et al, 2005; Langrish et al, 2005). Unbalanced Th1/Th2 T-cell polarization has been suggested to play a pathogenetic role in the development of autoimmune diseases. Modulation of T-cell polarization is a potential therapeutic target in the various autoimmune diseases
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