Intravenous immunoglobulin (IVIg) acts directly on conventional T cells to suppress T cell receptor signaling
Intravenous immunoglobulin (IVIg) acts directly on conventional T cells to suppress T cell receptor signaling
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静脉注射免疫球蛋白 (IVIg) 直接作用于常规 T 细胞，抑制 T 细胞受体信号传导
DOI：
10.1016/j.bbrc.2019.11.169
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发表时间：
2020
影响因子：
3.1
通讯作者：
Kawamoto Seiji
中科院分区：
文献类型：
--
作者：
Hori Ayane;Fujimura Takashi;Murakami Mai;Park Jungyeon;Kawamoto Seiji
静脉注射免疫球蛋白（IVIg）疗法广泛用于治疗自身免疫性疾病和感染性疾病。尽管 IVIg 治疗具有临床疗效，但其精确的免疫抑制机制仍不清楚。在这里，我们提供的证据表明 IVIg 直接作用于 T 细胞，抑制 T 细胞受体 (TCR) 连接后的激活。 IVIg 在抗 CD3 抗体和 T 细胞促有丝分裂原刺激后抑制小鼠脾细胞的增殖。 IVIg 的这些免疫抑制作用对于纯化的 T 细胞来说仍然是完整的，并且天然存在的调节性 T 细胞 (nTreg) 的消耗对 T 细胞的调节活性没有影响。相反，我们发现 IVIg 负向调节 TCR 信号传导； IVIg 共刺激会损害 IκB 降解、活化 T 细胞核因子 (NFAT) 的核转位以及丝裂原激活蛋白激酶（MAPK、Erk1/2）的激活。这些结果表明 IVIg 具有额外的新免疫抑制作用，它直接作用于常规 T 细胞以抑制 TCR 信号通路。
Intravenous immunoglobulin (IVIg) therapy is widely used to treat autoimmune and infectious disorders. Despite the clinical efficacy of IVIg therapy, its precise immunosuppressive mechanisms remain unclear. Here, we provide evidence that IVIg acts directly on T cells to suppress their activation upon T cell receptor (TCR) ligation. IVIg suppressed the proliferation of murine splenocytes upon stimulation with anti-CD3 antibody and T cell-tropic mitogens. These immunosuppressive effects of IVIg were still intact against purified T cells, and the depletion of naturally-occurring regulatory T cells (nTreg) had no effect on T cell regulatory activity. Instead, we found that IVIg negatively regulated TCR signaling; IVIg co-stimulation impaired IκB degradation, nuclear translocation of the nuclear factor of activated T cells (NFAT), and the activation of mitogen-activated protein kinase (MAPK, Erk1/2). These results suggest an additional new immunosuppressive role of IVIg, which acts directly on conventional T cells to suppress the TCR signaling pathway.