CD8+CD122+ Regulatory T Cells (Tregs) and CD4+ Tregs Cooperatively Prevent and Cure CD4+ Cell-Induced Colitis

CD8+CD122+ Regulatory T Cells (Tregs) and CD4+ Tregs Cooperatively Prevent and Cure CD4+ Cell-Induced Colitis
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DOI:
10.4049/jimmunol.1000800
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发表时间:
2011-01-01
影响因子:
4.4
通讯作者:
Suzuki, Haruhiko
Suzuki, Haruhiko
中科院分区:
医学2区
文献类型:
--
作者:
Endharti, Agustina Tri;Okuno, Yusuke;Suzuki, Haruhiko

文献摘要

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我们鉴定了CD 8(+)CD 122(+)调节性T细胞(TCRs),并证明了它们在维持免疫稳态和从实验性自身免疫性脑脊髓炎恢复中的重要性。在这篇论文中,我们证明了CD 8(+)CD 122(+)T细胞在小鼠模型中有效地预防和治疗结肠炎。在我们的实验中,通过转移用CD 4(+)T淋巴细胞排除的CD 4(+)CD 45 RB(高)细胞,在淋巴细胞缺陷的RAG-2(-/-)小鼠中诱导结肠炎。CD 8(+)CD 122(+)细胞的共转移明显抑制了结肠炎的发展,这种抑制作用与主要为CD 4(+)T细胞的CD 4(+)CD 45 RB(低)细胞的抑制作用相似。从IL-10(-/-)小鼠获得的CD 8(+)CD 122(+)细胞不能抑制结肠炎,表明IL-10是抑制结肠炎的重要效应传递因子。CD 8(+)CD 122(+)细胞在CD 4(+)CD 45 RB(high)细胞后4 wk时显示出抑制作用,表明CD 8(+)CD 122(+)细胞的治疗潜力。CD 8(+)CD 122(+)细胞和CD 4(+)CD 45 RB(低)细胞的混合物远比单一的TCLs有效,表明这些TCLs的协同作用。这些总体研究结果表明,CD 8(+)T淋巴细胞,并可能与CD 4 + T淋巴细胞,在炎症性肠病患者的医疗保健的潜在作用。免疫学杂志,2011,186:41-52。
We identified CD8(+)CD122(+) regulatory T cells (Tregs) and demonstrated their importance in the maintenance of immune homeostasis and in the recovery from experimental autoimmune encephalomyelitis. In this paper, we show that CD8(+)CD122(+) Tregs effectively prevent and cure colitis in a mouse model. In our experiments, colitis was induced in lymphocyte-deficient RAG-2(-/-) mice by transferring CD4(+)CD45RB(high) cells that were excluded with CD4(+) Tregs. Cotransfer of CD8(+)CD122(+) cells clearly suppressed the development of colitis, and this suppressive effect was similar to that of CD4(+)CD45RB(low) cells that were mostly CD4(+) Tregs. CD8(+)CD122(+) cells obtained from IL-10(-/-) mice were unable to suppress colitis, indicating that IL-10 is an important effect-transmitting factor in the suppression of colitis. CD8(+)CD122(+) cells showed a suppressive effect when they were transferred 4 wk after CD4(+)CD45RB(high) cells, indicating the therapeutic potential of CD8(+)CD122(+) cells. A mixture of CD8(+)CD122(+) cells and CD4(+)CD45RB(low) cells was far more effective than single Tregs, indicating the synergistic effect of these Tregs. These overall findings demonstrate the potential role of CD8(+) Tregs, and possibly together with CD4+ Tregs, in the medical care of inflammatory bowel disease patients. The Journal of Immunology, 2011, 186: 41-52.