Preventing autoimmune arthritis using antigen-specific immature dendritic cells: a novel tolerogenic vaccine.
Preventing autoimmune arthritis using antigen-specific immature dendritic cells: a novel tolerogenic vaccine.
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DOI：
10.1186/ar2031
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发表时间：
2006
影响因子：
4.9
通讯作者：
Min, Wei-Ping
中科院分区：
文献类型：
--
作者：
Popov, Igor;Li, Mu;Zheng, Xiufen;San, Hongtao;Zhang, Xusheng;Ichim, Thomas E;Suzuki, Motohiko;Feng, Biao;Vladau, Costin;Zhong, Robert;Garcia, Bertha;Strejan, Gill;Inman, Robert D;Min, Wei-Ping
自身免疫性疾病的常规治疗严重依赖于非特异性免疫抑制剂，其具有多种不良反应，而不会以特定方式抑制自身免疫过程。在本研究中，我们证明了抗原特异性，成熟抗性，致耐受性树突状细胞（DC）在抑制胶原诱导的关节炎，类风湿性关节炎的小鼠模型的有效性。用NF-κB抑制剂LF 15-0195（LF）处理DC祖细胞产生致耐受性DC群体，其特征在于MHC II类、CD 40和CD 86分子的低表达，以及在混合白细胞反应中的不良同种异体刺激能力。将LF处理的DC用钥孔血蓝蛋白抗原脉冲给幼稚小鼠导致对该抗原的特异性低反应性。此外，LF处理的DC与胶原诱导的关节炎的小鼠的管理导致在一个改善的临床评分，在抑制抗原特异性T细胞反应，并在减少抗体反应的胶原。通过组织学检查证实了LF处理的DC在预防关节炎中的功效，其揭示了关节中炎性细胞浸润的显著减少。总之，我们证明，在体外产生的抗原特异性的未成熟DC可能有重要的潜力，作为一种耐受性疫苗治疗自身免疫性关节炎。
Conventional treatments for autoimmune diseases have relied heavily on nonspecific immune suppressants, which possess a variety of adverse effects without inhibiting the autoimmune process in a specific manner. In the present study we demonstrate the effectiveness of antigen-specific, maturation-resistant, tolerogenic dendritic cells (DC) in suppressing collagen-induced arthritis, a murine model of rheumatoid arthritis. Treatment of DC progenitors with the NF-κB inhibiting agent LF 15-0195 (LF) resulted in a population of tolerogenic DC that are characterized by low expression of MHC class II, CD40, and CD86 molecules, as well as by poor allostimulatory capacity in a mixed leukocyte reaction. Administering LF-treated DC pulsed with keyhole limpet hemocyanin antigen to naïve mice resulted hyporesponsiveness specific for this antigen. Furthermore, administration of LF-treated DC to mice with collagen-induced arthritis resulted in an improved clinical score, in an inhibited antigen-specific T-cell response, and in reduced antibody response to the collagen. The efficacy of LF-treated DC in preventing arthritis was substantiated by histological examination, which revealed a significant decrease in inflammatory cell infiltration in the joints. In conclusion, we demonstrate that in vitro-generated antigen-specific immature DC may have important potential as a tolerogenic vaccine for the treatment of autoimmune arthritis.