IL-6-dependent spontaneous proliferation is required for the induction of colitogenic IL-17-producing CD8+ T cells.
IL-6-dependent spontaneous proliferation is required for the induction of colitogenic IL-17-producing CD8+ T cells.
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DOI：
10.1084/jem.20071133
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发表时间：
2008-05-12
期刊：
影响因子：
--
通讯作者：
Nishimura T
中科院分区：
文献类型：
--
作者：
Tajima M;Wakita D;Noguchi D;Chamoto K;Yue Z;Fugo K;Ishigame H;Iwakura Y;Kitamura H;Nishimura T
我们提出了一种新的作用，白细胞介素（IL）6诱导幼稚的CD 8 + T细胞，这是一个关键的步骤，在大肠杆菌的CD 8 + T细胞的分化的快速自发增殖（SP）。T细胞的稳态由两种不同的细胞增殖模式调节：主要组织相容性复合物/抗原驱动的快速SP和IL-7/IL-15依赖的缓慢稳态增殖。使用我们的CD 8 + T细胞依赖性结肠炎的新模型，我们发现初始CD 8 + T细胞的SP对于诱导致病性产生精氨酸的效应T细胞是必需的。在肠道植物群和IL-6的影响下，快速SP主要在肠系膜淋巴结（LN）中诱导，而在外周LN中不诱导。事实上，该SP被抗IL-6受体单克隆抗体（IL-6 R mAb）或抗真菌诱导的植物群耗竭显著抑制，但不被抗IL-7 R mAb和/或在IL-15缺乏条件下抑制。在抑制SP的同时，抗IL-6 R mAb显著抑制CD 8 + T细胞依赖性自身免疫性结肠炎的诱导。值得注意的是，来自IL-17−/−小鼠的初始CD 8 + T细胞的转移不会诱导自身免疫性结肠炎。因此，我们得出结论，IL-6信号是至关重要的SP淋巴细胞减少的条件下，随后导致严重的IL-17产生的CD 8 + T细胞介导的自身免疫性结肠炎。因此，抗IL-6 R单克隆抗体有望成为结肠炎治疗的一种新方法。
We propose a novel role for interleukin (IL) 6 in inducing rapid spontaneous proliferation (SP) of naive CD8+ T cells, which is a crucial step in the differentiation of colitogenic CD8+ T cells. Homeostasis of T cells is regulated by two distinct modes of cell proliferation: major histocompatibility complex/antigen–driven rapid SP and IL-7/IL-15–dependent slow homeostatic proliferation. Using our novel model of CD8+ T cell–dependent colitis, we found that SP of naive CD8+ T cells is essential for inducing pathogenic cytokine-producing effector T cells. The rapid SP was predominantly induced in mesenteric lymph nodes (LNs) but not in peripheral LNs under the influence of intestinal flora and IL-6. Indeed, this SP was markedly inhibited by treatment with anti–IL-6 receptor monoclonal antibody (IL-6R mAb) or antibiotic-induced flora depletion, but not by anti–IL-7R mAb and/or in IL-15–deficient conditions. Concomitantly with the inhibition of SP, anti–IL-6R mAb significantly inhibited the induction of CD8+ T cell–dependent autoimmune colitis. Notably, the transfer of naive CD8+ T cells derived from IL-17−/− mice did not induce autoimmune colitis. Thus, we conclude that IL-6 signaling is crucial for SP under lymphopenic conditions, which subsequently caused severe IL-17–producing CD8+ T cell–mediated autoimmune colitis. We suggest that anti–IL-6R mAb may become a promising strategy for the therapy of colitis.
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白介素（IL）-15和IL-7联合调节记忆表型CD8+细胞的体内稳态增殖，但对于记忆表型CD4+细胞不需要。
影响因子：
15.3
作者：
Tan, Joyce T;Ernst, Bettina;Kieper, William C;LeRoy, Eric;Sprent, Jonathan;Surh, Charles D
通讯作者：
Surh, Charles D
影响因子：
15.9
作者：
Fuss, IJ;Heller, F;Strober, W
通讯作者：
Strober, W
影响因子：
82.9
作者：
Atreya, R;Mudter, J;Neurath, MF
通讯作者：
Neurath, MF
影响因子：
64.5
作者：
King, C;Ilic, A;Sarvetnick, N
通讯作者：
Sarvetnick, N
影响因子：
4.4
作者：
Takaoka, A;Tanaka, Y;Nishimura, T
通讯作者：
Nishimura, T