Promoting tolerance to proteolipid protein-induced experimental autoimmune encephalomyelitis through targeting dendritic cells
Promoting tolerance to proteolipid protein-induced experimental autoimmune encephalomyelitis through targeting dendritic cells
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DOI：
10.1073/pnas.1010263107
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发表时间：
2010-10-05
影响因子：
11.1
通讯作者：
Strominger, Jack L.
中科院分区：
文献类型：
--
作者：
Stern, Joel N. H.;Keskin, Derin B.;Strominger, Jack L.
在T细胞介导的自身免疫性疾病中，具有已知抗原特异性的自反应性T细胞似乎是抗原特异性诱导耐受性的特别有希望的靶标，而不会损害期望的保护性宿主免疫反应。一些证据表明，在稳定状态下将抗原递送到抗原呈递的树突状细胞（dc）（即未成熟的dc）可能是一种诱导抗原特异性t细胞外周耐受的合适方法。在这里，我们报道了抗dec205介导的自肽蛋白脂质蛋白（PLP） 139-151递送到DCs改善了PLP诱导的实验性自身免疫性脑脊髓炎SJL模型的临床症状。经处理的小鼠脾细胞被灌注到PLP139-151， IL-17的分泌明显减少。此外，我们使用PLP139-151特异性的转基因CD4(+) V β 6(+) TCR T细胞直接表明，在本实验条件下，这些细胞也成为无能细胞。此外，还获得了CD4(+) T细胞介导的抑制机制的证据。
In T cell-mediated autoimmune diseases, self-reactive T cells with known antigen specificity appear to be particularly promising targets for antigen-specific induction of tolerance without compromising desired protective host immune responses. Several lines of evidence suggest that delivery of antigens to antigen-presenting dendritic cells (DCs) in the steady state (i.e., to immature DCs) may represent a suitable approach to induce antigen-specific T-cell tolerance peripherally. Here, we report that anti-DEC205-mediated delivery of the self-peptide proteolipid protein (PLP) 139-151 to DCs ameliorated clinical symptoms in the PLP-induced SJL model of experimental autoimmune encephalomyelitis. Splenocytes from treated mice were anergized to PLP139-151, and IL-17 secretion was markedly reduced. Moreover, we show directly, using transgenic CD4(+) V beta 6(+) TCR T cells specific for PLP139-151, that, under the conditions of the present experiments, these cells also became anergic. In addition, evidence for a CD4(+) T cell-mediated suppressor mechanism was obtained.