IL-18 together with anti-CD3 antibody induces human Th1 cells to produce Th1- and Th2-cytokines and IL-8
IL-18 together with anti-CD3 antibody induces human Th1 cells to produce Th1- and Th2-cytokines and IL-8
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DOI：
10.1093/intimm/dxh174
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发表时间：
2004-12-01
影响因子：
4.4
通讯作者：
Nakanishi, K
中科院分区：
文献类型：
--
作者：
Hata, H;Yoshimoto, T;Nakanishi, K
尽管 IL-18 最初被认为是增强 Th1 细胞产生 IFN-γ 的因子，但后来的研究揭示了其诱导 T 细胞、NK 细胞和嗜碱性粒细胞/肥大细胞产生 Th2 细胞因子的潜力。最近，我们证明，当鼻腔给予 Ag 和 IL-18 刺激宿主小鼠中转移的细胞时，被动转移的记忆表型 Th1 细胞会产生 Th1-、Th2-细胞因子、GM-CSF 和趋化因子，从而诱导宿主小鼠气道炎症和高反应性。此外，IL-18 被认为会导致人类患者哮喘恶化。因此，确定人 Th1 细胞在体外用抗 CD3 和 IL-18 刺激时是否也有可能产生这些可溶性因子非常重要。在这里，我们证明，在用抗CD3和IL-18刺激后，只有Th1细胞而不是Th2细胞产生IFN-γ、IL-13、GM-CSF和IL-8。此外，高度纯化的产生 IFN-γ 的 Th1 细胞也具有相同的潜力。因此，当体内Ag和IL-18刺激时，人类Th1细胞可能变成非常有害的细胞，并产生IFN-γ、IL-13、GM-CSF和IL-8，它们组合起来可能诱发严重的炎症，例如气道炎症。
Although IL-18 was initially regarded as a factor that enhances IFN-gamma production from Th1 cells, later studies revealed its potential to induce Th2 cytokine production from T cells, NK cells and basophils/mast cells. Very recently, we demonstrated that passively transferred memory phenotype Th1 cells induce airway inflammation and hyperresponsiveness in a host mouse by production of Th1-, Th2-cytokines, GM-CSF and chemokines, when the transferred cells are stimulated in the host mice with nasally administered Ag and IL-18. Moreover, IL-18 is suggested to contribute to asthma exacerbation in human patients. Therefore, it is important to determine whether human Th1 cells also have the potential to produce these soluble factors when stimulated with anti-CD3 and IL-18 in vitro. Here we demonstrated that only Th1 cells, but not Th2 cells, produce IFN-gamma, IL-13, GM-CSF and IL-8 after stimulation with anti-CD3 and IL-18. Furthermore, highly purified IFN-gamma-producing Th1 cells have the same potential. Thus, human Th1 cells may become very harmful cells, when stimulated with Ag and IL-18 in vivo, and produce IFN-gamma, IL-13, GM-CSF and IL-8, which in combination might induce severe inflammation such as airway inflammation.