Gordon John R, Li Fang, Nayyar Aarti, Xiang Jim, Zhang Xiaobei
Immunology Research Group, Department of Veterinary Microbiology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
J Immunol. 2005 Aug 1;175(3):1516-22. doi: 10.4049/jimmunol.175.3.1516.
Splenic CD8alpha+ dendritic cells reportedly tolerize T cell responses by inducing Fas ligand-mediated apoptosis, suppressing IL-2 expression, or catabolizing T cell tryptophan reserves through expression of IDO. We report in this study that CD8alpha+, but not CD8alpha-, dendritic cells purified from the spleens of normal mice can tolerize the Th2 responses of cells from asthma phenotype mice through more than one mechanism. This tolerance could largely be reversed in vitro by anti-IL-10 or anti-TGFbeta Ab treatment. However, loss of direct dendritic cell-T cell contact also reduced tolerance, although to a lesser extent, as did adding the IDO inhibitor 1-methyltryptophan or an excess of free tryptophan to the cultures. Within 3 wk of reconstituting asthma phenotype mice with 1 x 10(5) OVA-pulsed CD8alpha+, but not CD8alpha-, dendritic cells, the mice experienced a reversal of airway hyperresponsiveness, eosinophilic airway responses, and pulmonary Th2 cytokine expression. This data indicates that CD8alpha+ dendritic cells can simultaneously use multiple mechanisms for tolerization of T cells and that, in vivo, they are capable of tolerizing a well-established disease complex such as allergic lung disease/asthma.
据报道，脾脏CD8α⁺树突状细胞通过诱导Fas配体介导的细胞凋亡、抑制IL-2表达或通过吲哚胺2,3-双加氧酶（IDO）的表达分解代谢T细胞色氨酸储备来使T细胞反应产生耐受。我们在本研究中报告，从正常小鼠脾脏中纯化的CD8α⁺而非CD8α⁻树突状细胞可通过多种机制使哮喘表型小鼠的细胞产生Th2反应耐受。这种耐受性在体外可通过抗IL-10或抗TGFβ抗体处理在很大程度上被逆转。然而，直接的树突状细胞 - T细胞接触的丧失也会降低耐受性，尽管程度较小，向培养物中添加IDO抑制剂1 - 甲基色氨酸或过量的游离色氨酸时也是如此。在用1×10⁵个卵清蛋白（OVA）脉冲处理的CD8α⁺而非CD8α⁻树突状细胞重建哮喘表型小鼠3周内，小鼠的气道高反应性、嗜酸性气道反应和肺部Th2细胞因子表达出现逆转。该数据表明，CD8α⁺树突状细胞可同时利用多种机制使T细胞产生耐受，并且在体内，它们能够使诸如过敏性肺病/哮喘等已确立的疾病复合体产生耐受。
