Glatiramer acetate ameliorates inflammatory bowel disease in mice through the induction of Qa‐1‐restricted CD8+ regulatory cells
Glatiramer acetate ameliorates inflammatory bowel disease in mice through the induction of Qa‐1‐restricted CD8+ regulatory cells
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DOI：
10.1002/eji.201242758
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发表时间：
2013-01
影响因子：
5.4
通讯作者：
Yunliang Yao;W. Han;Jingjing Liang;J. Ji;Jianli Wang;H. Cantor;Linrong Lu
中科院分区：
文献类型：
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作者：
Yunliang Yao;W. Han;Jingjing Liang;J. Ji;Jianli Wang;H. Cantor;Linrong Lu
炎症性肠病（IBD）是一种复杂的多因素免疫性疾病，其特征是肠道免疫反应失调。在这里，我们研究了 Qa-1 限制性 CD8+ Treg 细胞在调节小鼠实验性 IBD 中的作用。我们发现，通过 T 细胞疫苗接种诱导的 CD8+ T 细胞过继转移至 IBD 小鼠后，可改善右旋糖酐硫酸钠诱导的 IBD 的病理表现。此外，接种醋酸格拉替雷 (GA) 疫苗可诱导 CD8+ 细胞抑制活性，GA 是 FDA 批准的治疗多发性硬化症 (MS) 的药物。接下来我们发现 GA 诱导的 CD8+ Treg 细胞以 Qa-1 依赖性方式发挥作用，其抑制活性取决于穿孔素介导的细胞毒性。最后，我们证实了CD4+ T细胞在葡聚糖硫酸钠诱导的结肠炎进展中的作用，并阐明了GA诱导的CD8+ T细胞通过靶向致病性CD4+ T细胞对结肠炎发挥治疗作用。我们的结果揭示了 Qa-1 限制性 CD8+ Treg 细胞在 IBD 中的新调节作用，并表明通过 GA 疫苗接种诱导它们作为 IBD 的潜在治疗方法。
Inflammatory bowel diseases (IBDs) are complex multifactorial immunological disorders characterized by dysregulated immune reactivity in the intestine. Here, we investigated the contribution of Qa‐1‐restricted CD8+ Treg cells in regulating experimental IBD in mice. We found that CD8+ T cells induced by T‐cell vaccination ameliorated the pathological manifestations of dextran sulfate sodium induced IBD when adoptively transferred into IBD mice. In addition, CD8+ cell suppressive activity was induced by vaccination with glatiramer acetate (GA), an FDA‐approved drug for multiple sclerosis (MS). We next showed that GA‐induced CD8+ Treg cells worked in a Qa‐1‐dependent manner and their suppressive activity depends on perforin‐mediated cytotoxicity. Finally, we confirmed the role of CD4+ T cells in dextran sulfate sodium induced colitis progression, and clarified that GA‐induced CD8+ T cells exerted their therapeutic effects on colitis by targeting pathogenic CD4+ T cells. Our results reveal a new regulatory role of Qa‐1‐restricted CD8+ Treg cells in IBD and suggest their induction by GA vaccination as a potential therapeutic approach to IBD.