Mucosal T cells bearing TCRγδ play a protective role in intestinal inflammation
Mucosal T cells bearing TCRγδ play a protective role in intestinal inflammation
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DOI：
10.4049/jimmunol.173.2.1390
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发表时间：
2004-07-15
影响因子：
4.4
通讯作者：
Yoshimura, A
中科院分区：
文献类型：
--
作者：
Inagaki-Ohara, K;Chinen, T;Yoshimura, A
携带TCR γ δ的肠上皮内淋巴细胞（IEL）代表鼠肠道中的主要T细胞群体。然而，γ δ IEL在炎症性肠病（IBD）中的作用仍然存在争议。在这项研究中，我们表明，γ δ IEL是一个重要的保护性T细胞群体对IBD。γ δ T细胞缺陷（CS-/-）小鼠随着年龄的增长发生自发性结肠炎，并且在年轻时对Th 1型2，4，6-三硝基苯磺酸（TNBS）诱导的结肠炎表现出高易感性。将gammadelta IEL转移至Cdelta（-/-）小鼠可改善TNBS诱导的结肠炎，这与IEL产生的IFN-γ和TNF-α的减少以及TGF-β的增加相关。此外，TNBS处理的Cdelta（-/-）小鼠的肠上皮细胞（EC）中表达的高水平IL-15（抑制激活诱导的细胞死亡以终止炎症）多于野生型小鼠。来自野生型小鼠的EC显著抑制TNBS处理的Cdelta（-/-）小鼠的IEL的IFN-γ产生，而来自TNBS处理的Cdelta（-/-）小鼠的EC没有。这些数据表明，γ δ IEL通过调节粘膜T细胞活化协同EC功能在控制IBD中发挥重要作用。我们的研究表明，增强调节性γ δ T细胞活性是一种可能的新的结肠炎细胞疗法。
Intestinal intraepithelial lymphocytes (IEL) bearing TCRgammadelta represent a major T cell population in the murine intestine. However, the role of gammadelta IEL in inflammatory bowel diseases (IBD) remains controversial. In this study, we show that gammadelta IEL is an important protective T cell population against IBD. gammadelta T cell-deficient (CS-/-) mice developed spontaneous colitis with age and showed high susceptibility to Th1-type 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis at a young age. Transfer of gammadelta IEL to Cdelta(-/-) mice ameliorated TNBS-induced colitis, which correlated with decrease of IFN-gamma and TNF-alpha production and an increase of TGF-beta production by IEL. Furthermore, a high level of IL-15, which inhibits activation-induced cell death to terminate inflammation, was expressed more in intestinal epithelial cells (EC) from TNBS-treated Cdelta(-/-) mice than in those from wild-type mice. EC from wild-type mice significantly suppressed the IFN-gamma production of IEL from TNBS-treated Cdelta(-/-) mice, whereas EC from TNBS-treated Cdelta(-/-) mice did not. These data indicate that gammadelta IEL play important roles in controlling IBD by regulating mucosal T cell activation cooperated with EC function. Our study suggests that enhancement of regulatory gammadelta T cell activity is a possible new cell therapy for colitis.