A role for NK cells as regulators of CD4+ T cells in a transfer model of colitis.
A role for NK cells as regulators of CD4+ T cells in a transfer model of colitis.
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NK 细胞在结肠炎转移模型中作为 CD4 T 细胞调节剂的作用。
DOI：
10.4049/jimmunol.161.7.3256
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发表时间：
1998
影响因子：
4.4
通讯作者：
D. Rennick
中科院分区：
文献类型：
--
作者：
M. Fort;M. Leach;D. Rennick
以往的研究表明，IL-10基因缺陷(IL-10(-/-))小鼠结肠的慢性炎症是由CD4+Th1 T细胞介导的，其最初的发育依赖于干扰素-γ的存在。由于来自IL-10(-/-)小鼠的CD4+T细胞被转移到重组酶激活基因(RAG)缺陷的受体体内会导致结肠炎，我们认为受体的NK细胞可能是结肠炎发生发展过程中干扰素-γ的重要来源。因此，测试了IL-10(-/-)CD4+T细胞在RAG缺陷的受体中引起结肠炎的能力，这些受者已经耗尽了NK细胞。与我们的预期相反，接受IL-10(-/-)CD4+T细胞的NK细胞耗竭的受者与未耗尽的受者相比，发展为加速疾病。此外，来自正常小鼠的CD4+T细胞(IL-10(+/+))也会在NK细胞耗尽的受体小鼠中引起结肠炎，但在非耗尽的受体小鼠中不会。NK细胞抑制效应细胞CD4+CD45RBHigh T细胞，随后的实验表明这种作用依赖于穿孔素。因此，NK细胞可以通过控制效应T细胞对肠道细菌的反应，在下调Th1介导的结肠炎中发挥重要作用。
Previous studies have shown that the chronic inflammation observed in the colon of IL-10-deficient (IL-10(-/-)) mice is mediated by CD4+ Th1 T cells and is dependent on the presence of IFN-gamma for its initial development. As CD4+ T cells from IL-10(-/-) mice will cause colitis when transferred into recombinase-activating gene (Rag)-deficient recipients, we considered the possibility that the recipients' NK cells could be an important source of IFN-gamma for the development of colitis. Therefore, the ability of IL-10(-/-) CD4+ T cells to cause colitis in Rag-deficient recipients that had been depleted of NK cells was tested. Contrary to our expectations, NK cell-depleted recipients of IL-10(-/-) CD4+ T cells developed accelerated disease compared with nondepleted recipients. Furthermore, CD4+ T cells from normal mice (IL-10(+/+)) also caused colitis in NK cell-depleted recipient mice, but not in nondepleted recipients. NK cells inhibited effector CD4+CD45RBhigh T cells, and subsequent experiments showed that this effect was dependent on perforin. Thus NK cells can play an important role in down-regulating Thl-mediated colitis by controlling the responses of effector T cells to gut bacteria.