Mast cells control neutrophil recruitment during T cell-mediated delayed-type hypersensitivity reactions through tumor necrosis factor and macrophage inflammatory protein 2.
Mast cells control neutrophil recruitment during T cell-mediated delayed-type hypersensitivity reactions through tumor necrosis factor and macrophage inflammatory protein 2.
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肥大细胞通过肿瘤坏死因子和巨噬细胞炎症蛋白2控制T细胞介导的延迟型超敏反应期间的中性粒细胞募集。
DOI：
10.1084/jem.192.10.1441
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发表时间：
2000-11-20
影响因子：
15.3
通讯作者：
Rocken, M
中科院分区：
文献类型：
--
作者：
Biedermann, T;Kneilling, M;Mailhammer, R;Maier, K;Sander, C A;Kollias, G;Kunkel, S L;Hultner, L;Rocken, M
中性粒细胞(PMN)是T细胞介导的自身免疫性疾病和皮肤、关节和肠道的迟发型超敏反应(DTHR)的病理特征，但在脑或胰腺的T细胞介导的自身免疫性疾病中不存在。所有这些反应都是由产生干扰素γ的1型T细胞介导的，并产生类似的细胞因子模式。因此，在DTHR过程中，负责PMN重新募集到皮肤、关节或肠道的细胞和介质仍然未知。通过分析半抗原诱导的皮肤DTHRs，我们发现肥大细胞通过肿瘤坏死因子和CXC趋化因子巨噬细胞炎性蛋白2(MIP-2)两种媒介决定T细胞依赖的PMN募集，MIP-2是人白介素8的功能类似物。在野生型(WT)小鼠的DTHRs中，可提取的MIP-2蛋白丰富，而在肥大细胞缺陷WBB6F1-KitW/KitW-v(KitW/KitW-v)小鼠中则不存在。在肥大细胞缺陷的KitW/KitW-v小鼠中，抗MIP-2抗体使T细胞依赖的PMN募集减少了60%，而肥大细胞缺陷的KitW/KitW-v小鼠减少了80%。来自WT小鼠的肥大细胞有效地恢复了kitw/kitw-v小鼠的DTHR和MIP2依赖的中性粒细胞募集，而来自肿瘤坏死因子−/−小鼠的肥大细胞则不能。因此，肥大细胞来源的肿瘤坏死因子和MIP-2最终决定了T细胞介导的DTHR中细胞的浸润模式。
Polymorphonuclear leukocytes (PMNs) characterize the pathology of T cell–mediated autoimmune diseases and delayed-type hypersensitivity reactions (DTHRs) in the skin, joints, and gut, but are absent in T cell–mediated autoimmune diseases of the brain or pancreas. All of these reactions are mediated by interferon γ–producing type 1 T cells and produce a similar pattern of cytokines. Thus, the cells and mediators responsible for the PMN recruitment into skin, joints, or gut during DTHRs remain unknown. Analyzing hapten-induced DTHRs of the skin, we found that mast cells determine the T cell–dependent PMN recruitment through two mediators, tumor necrosis factor (TNF) and the CXC chemokine macrophage inflammatory protein 2 (MIP-2), the functional analogue of human interleukin 8. Extractable MIP-2 protein was abundant during DTHRs in and around mast cells of wild-type (WT) mice but absent in mast cell–deficient WBB6F1-KitW/KitW- v (KitW/KitW -v) mice. T cell–dependent PMN recruitment was reduced >60% by anti–MIP-2 antibodies and >80% in mast cell–deficient KitW/KitW -v mice. Mast cells from WT mice efficiently restored DTHRs and MIP-2–dependent PMN recruitment in KitW/KitW-v mice, whereas mast cells from TNF−/− mice did not. Thus, mast cell–derived TNF and MIP-2 ultimately determine the pattern of infiltrating cells during T cell–mediated DTHRs.