The First Ward in Department of Neurology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Xinxiang, Henan Province 453100, PR China.
The First Ward in Department of Neurology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Xinxiang, Henan Province 453100, PR China.
Int Immunopharmacol. 2019 Oct;75:105773. doi: 10.1016/j.intimp.2019.105773. Epub 2019 Jul 23.
Enterovirus 71 (EV71) always induces severe hand, foot, and mouth disease with neurological complications, such as encephalitis. Interleukin (IL)-7 augments CD8 T cells activity in chronic viral infection and cancers. However, few studies have focused on common γ-chain (γc) cytokine expression and regulatory function of IL-7 to CD8 T cells in EV71 associated encephalitis. In this study, twenty-one patients with EV71 associated encephalitis, twenty-seven patients with febrile convulsion (FC), and twenty healthy individuals were enrolled. γc cytokine (IL-2, IL-4, IL-7 and IL-15) concentration was measured by ELISA. IL-7 receptor α chain (membrane/soluble CD127) expression was also investigated. Purified CD8 T cells were stimulated with recombinant human IL-7 in vitro. The regulatory activity of IL-7 to CD8 T cells from peripheral blood and cerebrospinal fluids (CSF) was investigated in direct and indirect contact co-culture with U-87MG cells. IL-7 in the serum and CSF, but not IL-2, IL-4, or IL-15, was significant increased in EV71 associated encephalitis. Both total CD127 mRNA relative level and membrane/soluble CD127 expression was comparable among three groups. IL-7 stimulation promoted CD8 T cells proliferation, up-regulated perforin/granzyme B level, but reduced programmed death-1 expression in CD8 T cells from EV71 associated encephalitis patients. Cytotoxicity and interferon-γ production of CD8 T cells from peripheral blood and CSF was also augmented in response to IL-7 stimulation in both direct and indirect co-culture systems in EV71 associated encephalitis. The present data indicated that IL-7 induced cytolytic and non-cytolytic functions of CD8 T cells in EV71 associated encephalitis. IL-7 might be considered as one of the immunomodulatory therapeutic candidates for EV71 infection.
肠道病毒 71 型（EV71）可引起手足口病，并伴有神经并发症，如脑炎。白细胞介素（IL）-7 可增强慢性病毒感染和癌症中 CD8 T 细胞的活性。然而，很少有研究关注 EV71 相关脑炎中常见 γ 链（γc）细胞因子表达和 IL-7 对 CD8 T 细胞的调节功能。在这项研究中，纳入了 21 例 EV71 相关脑炎患者、27 例热性惊厥（FC）患者和 20 名健康个体。通过 ELISA 测定 γc 细胞因子（IL-2、IL-4、IL-7 和 IL-15）浓度。还研究了 IL-7 受体 α 链（膜/可溶性 CD127）的表达。体外用重组人 IL-7 刺激纯化的 CD8 T 细胞。在与 U-87MG 细胞直接和间接接触共培养中，研究了外周血和脑脊液（CSF）中 IL-7 对 CD8 T 细胞的调节活性。EV71 相关脑炎患者血清和 CSF 中 IL-7 明显升高，但 IL-2、IL-4 或 IL-15 无明显升高。三组间总 CD127 mRNA 相对水平和膜/可溶性 CD127 表达无差异。IL-7 刺激可促进 EV71 相关脑炎患者 CD8 T 细胞增殖，上调穿孔素/颗粒酶 B 水平，但降低 CD8 T 细胞程序性死亡-1 表达。在 EV71 相关脑炎中，直接和间接共培养系统中，IL-7 刺激还可增强外周血和 CSF 中 CD8 T 细胞的细胞毒性和干扰素-γ 产生。本研究表明，IL-7 诱导 EV71 相关脑炎中 CD8 T 细胞的细胞毒性和非细胞毒性功能。IL-7 可能被视为 EV71 感染的一种免疫调节治疗候选物。
