IL-15 通过上调 CCR5 表达增强记忆性 CD8 T 细胞的 CCR5 介导的迁移，而无需 TCR 刺激。
IL-15 enhances CCR5-mediated migration of memory CD8 T cells by upregulating CCR5 expression in the absence of TCR stimulation.
机构信息
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.
Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon 35015, Republic of Korea.
出版信息
Cell Rep. 2021 Jul 27;36(4):109438. doi: 10.1016/j.celrep.2021.109438.
During microbial infection, bystander CD8 T cells that are not specific to infecting pathogens can be activated by interleukin (IL)-15. However, the tissue-homing properties of bystander-activated CD8 T cells have not been elucidated. Here, we examine the effects of IL-15 on the expression of chemokine receptors on CD8 T cells and their migration. IL-15 upregulates CCR5 in memory CD8 T cells in the absence of T cell receptor (TCR) stimulation and enhances CCR5-dependent migration. IL-15-induced CCR5 upregulation is abrogated by TCR stimulation, indicating that CCR5 is upregulated in bystander-activated CD8 T cells. Moreover, CCR5 signals increase proliferation and cytotoxic protein expression in IL-15-treated memory CD8 T cells, although the increase has a small extent. CCR5 upregulation in bystander-activated CD8 T cells is associated with severe liver injury in patients with acute hepatitis A. Altogether, the results indicate that CCR5 upregulation by IL-15 mediates the migration of bystander-activated CD8 T cells.
在微生物感染过程中，非特异性针对感染病原体的旁观者 CD8 T 细胞可被白细胞介素 (IL)-15 激活。然而，旁观者激活的 CD8 T 细胞的组织归巢特性尚未阐明。在这里，我们研究了 IL-15 对 CD8 T 细胞上趋化因子受体表达及其迁移的影响。在没有 T 细胞受体 (TCR) 刺激的情况下，IL-15 上调记忆 CD8 T 细胞中的 CCR5，并增强 CCR5 依赖性迁移。TCR 刺激可消除 IL-15 诱导的 CCR5 上调，表明 CCR5 在旁观者激活的 CD8 T 细胞中上调。此外，CCR5 信号增加了 IL-15 处理的记忆 CD8 T 细胞中的增殖和细胞毒性蛋白表达，尽管增加幅度较小。急性甲型肝炎患者中旁观者激活的 CD8 T 细胞中 CCR5 的上调与严重的肝损伤有关。总的来说，这些结果表明，IL-15 介导的 CCR5 上调可调节旁观者激活的 CD8 T 细胞的迁移。
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