School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea.
Exp Mol Med. 2010 Mar 31;42(3):187-94. doi: 10.3858/emm.2010.42.3.019.
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.
胶原诱导关节炎(CIA)是由自身反应性 CD4(+)T 细胞介导的,这些细胞产生炎症细胞因子。已知 TGF-β(2)处理的耐受性抗原呈递细胞(Tol-APCs)可在各种自身免疫性疾病中诱导耐受。在这项研究中,我们研究了胶原特异性 Tol-APCs 是否可以诱导 CIA 的抑制。我们观察到 Tol-APCs 可以抑制 CIA 的发展和严重程度,并延迟 CIA 的发作。Tol-APCs 的治疗减少了体外胶原抗原刺激后 IFN-γ和 IL-17 产生的 CD4(+)T 细胞的数量,并增加了 IL-4 和 IL-5 产生的 CD4(+)T 细胞的数量。Tol-APCs 对 CIA 的抑制作用与它们选择性诱导 IL-10 产生的能力相关。我们还观察到,Tol-APCs 的治疗不仅抑制了 CIA 过程中的细胞免疫反应,也抑制了体液免疫反应。我们的结果表明,体外生成的 Tol-APCs 具有治疗类风湿关节炎和其他自身免疫性疾病的潜在治疗价值。