Protection against experimental autoimmune encephalomyelitis generated by a recombinant adenovirus vector expressing the Vβ8.2 TCR is disrupted by coadministration. with vectors expressing either IL-4 or-10
Protection against experimental autoimmune encephalomyelitis generated by a recombinant adenovirus vector expressing the Vβ8.2 TCR is disrupted by coadministration. with vectors expressing either IL-4 or-10
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DOI：
10.4049/jimmunol.170.2.765
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发表时间：
2003-01-15
影响因子：
4.4
通讯作者：
Kumar, V
中科院分区：
文献类型：
--
作者：
Braciak, TA;Pedersen, B;Kumar, V
腺病毒载体越来越多地用于基因疫苗接种，并且由于其产生高水平、瞬时基因表达的能力，可能非常适合干预不同的病理状况。在这项研究中，我们报告了使用重组腺病毒载体通过 TCR β 链的瞬时表达来诱导调节反应，从而预防自身免疫性疾病。用表达 TCR Vbeta8.2 链 (Ad5E1 mVbeta8.2) 的重组腺病毒对 B10.PL 小鼠进行免疫，诱导产生针对 Vbeta8.2 链 B5 肽 (aa 76-101) 内框架区 3 决定簇的调节性 1 型 CD4 T 细胞。该行列式很容易在环境 APC 上的 I-A(u) 上下文中处理和显示。 TCR Vbeta8.2 链的瞬时遗传传递可保护小鼠免受 Ag 诱导的实验性自身免疫性脑脊髓炎的影响。然而，当Ad5E1 mVbeta8.2载体与表达IL-4或IL-10的载体共同施用时，调节被破坏并且疾病加剧。这些结果强调了在实验性自身免疫性脑脊髓炎模型中有效调节性 T 细胞的生成和活性所必需的 Th1 样细胞因子需求的重要性。
Adenovirus vectors are increasingly being used for genetic vaccination and may prove highly suitable for intervention in different pathological conditions due to their capacity to generate high level, transient gene expression. In this study, we report the use of a recombinant adenovirus vector to induce regulatory responses for the prevention of autoimmune diseases through transient expression of a TCR beta-chain. Immunization of B10.PL mice with a recombinant adenovirus expressing the TCR Vbeta8.2 chain (Ad5E1 mVbeta8.2), resulted in induction of regulatory type 1 CD4 T cells, directed against the framework region 3 determinant within the B5 peptide (aa 76-101) of the Vbeta8.2 chain. This determinant is readily processed and displayed in an I-A(u) context, on ambient APC. Transient genetic delivery of the TCR Vbeta8.2 chain protected mice from Ag-induced experimental autoimmune encephalomyelitis. However, when the Ad5E1 mVbeta8.2 vector was coadministered with either an IL-4- or IL-10-expressing vector, regulation was disrupted and disease was exacerbated. These results highlight the importance of the Th1-like cytokine requirement necessary for the generation and activity of effective regulatory T cells in this model of experimental autoimmune encephalomyelitis.