Cell-contact-dependent activation of CD4+ T cells by adhesion molecules on synovial fibroblasts
Cell-contact-dependent activation of CD4+ T cells by adhesion molecules on synovial fibroblasts
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DOI：
10.1080/14397595.2016.1220353
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发表时间：
2017-01
影响因子：
2.2
通讯作者：
M. Mori;M. Hashimoto;T. Matsuo;T. Fujii;M. Furu;H. Ito;H. Yoshitomi;J. Hirose;Yoshinaga Ito;S. Akizuki;R. Nakashima;Y. Imura;N. Yukawa;H. Yoshifuji;K. Ohmura;T. Mimori
中科院分区：
文献类型：
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作者：
M. Mori;M. Hashimoto;T. Matsuo;T. Fujii;M. Furu;H. Ito;H. Yoshitomi;J. Hirose;Yoshinaga Ito;S. Akizuki;R. Nakashima;Y. Imura;N. Yukawa;H. Yoshifuji;K. Ohmura;T. Mimori
摘要目的：探讨滑膜成纤维细胞(SF)与细胞间接触对CD4+T细胞增殖和细胞因子产生的影响。方法：用抗CD3/2 8抗体刺激类风湿关节炎患者外周血中的天然CD_4~+T细胞，检测CD_4~+T细胞的增殖和干扰素-γ/IL-17的产生。为研究黏附分子的作用，用Transwell平板或抗细胞间黏附分子-1(ICAM-1)/血管细胞黏附分子-1(VCAM-1)抗体阻断细胞接触。为研究黏附分子对CD_4~+T细胞的直接作用，将CD_(161)+或CD_(161)-naive CD_4~+T细胞刺激于涂有重组细胞间黏附分子1或血管细胞黏附分子1的塑料平板上，分析干扰素-γ/IL-17的来源。结果：SF以细胞接触和部分ICAM-1/γ-1依赖的方式促进单纯CD_4+T细胞增殖和干扰素-ICAM-1/IL-17的产生。细胞间黏附分子-1和血管细胞黏附分子-1可促进初始CD_4+T细胞的增殖和干扰素-γ的产生，而血管细胞黏附分子-1则有效地促进IL-17的产生。CD161+单纯T细胞上调LFA-1和VLA-4是与ICAM-1/VCAM-1相互作用后产生γ/IL-17的主要来源。结论：CD_4~+T细胞通过黏附分子与SF接触后可迅速扩增并分泌干扰素-γ/IL-17。干预ICAM-1/VCAM-1可能有利于抑制RA滑膜炎症。
Abstract Objective: To determine how cell–cell contact with synovial fibroblasts (SF) influence on the proliferation and cytokine production of CD4+ T cells. Methods: Naïve CD4+ T cells were cultured with SF from rheumatoid arthritis patients, stimulated by anti-CD3/28 antibody, and CD4+ T cell proliferation and IFN-γ/IL-17 production were analyzed. To study the role of adhesion molecules, cell contact was blocked by transwell plate or anti-intracellular adhesion molecule-1 (ICAM-1)/vascular cell adhesion molecule-1(VCAM-1) antibody. To study the direct role of adhesion molecules for CD4+ T cells, CD161+ or CD161- naïve CD4+ T cells were stimulated on plastic plates coated by recombinant ICAM-1 or VCAM-1, and the source of IFN-γ/IL-17 were analyzed. Results: SF enhanced naïve CD4+ T cell proliferation and IFN-γ/IL-17 production in cell-contact and in part ICAM-1-/VCAM-1-dependent manner. Plate-coated ICAM-1 and VCAM-1 enhanced naïve CD4+ T cell proliferation and IFN-γ production, while VCAM-1 efficiently promoting IL-17 production. CD161+ naïve T cells upregulating LFA-1 and VLA-4 were the major source of IFN-γ/IL-17 upon interaction with ICAM-1/VCAM-1. Conclusion: CD4+ T cells rapidly expand and secrete IFN-γ/IL-17 upon cell-contact with SF via adhesion molecules. Interfering with ICAM-1-/VCAM-1 may be beneficial for inhibiting RA synovitis.