Department of Hematology, Shaanxi Provincial People's Hospital, The Affiliated Hospital of Xi'an Medical University, Xi'an, 710068, Shaanxi Province, China.
Department of Infectious Diseases, Shaanxi Provincial People's Hospital, The Affiliated Hospital of Xi'an Medical University, 256 West Youyi Rd, Xi'an, 710068, Shaanxi Province, China.
Arch Immunol Ther Exp (Warsz). 2022 Oct 11;70(1):25. doi: 10.1007/s00005-022-00663-8.
Interleukin (IL)-35 plays an immunosuppressive role in infectious diseases, autoimmune disorders, and cancers. However, IL-35 expression and its regulation of CD8 T cells in infectious mononucleosis (IM) are not fully understood. In this study, three groups of participants were compared, including twenty-three patients of IM without liver inflammation, twenty-eight patients of IM with liver inflammation, and twenty-one controls. Plasma and peripheral blood mononuclear cells (PBMCs) were isolated. CD8 T cells were purified. Plasma IL-35 was measured by ELISA. PBMCs and CD8 T cells were stimulated with recombinant human IL-35 in vitro. Perforin and granzyme B secretion was assessed by ELISPOT. Immune checkpoint molecule expression was investigated by flow cytometry. CD8 T cells were co-cultured with HepG2 cells in direct contact and indirect contact manner. The cytotoxicity of CD8 T cells was calculated by measuring lactate dehydrogenase release and proinflammatory cytokine expression. There was no significant difference in plasma IL-35 levels between patients with IM without liver inflammation and the controls, but the IL-35 level was notably increased in patients with IM who presented with liver inflammation and negatively correlated with aminotransferase. CD8 T cells in patients with IM with liver inflammation showed stronger cytotoxicity. IL-35 stimulation inhibited CD8 T cell-induced target cell death in patients with IM, mainly through suppression of IFN-γ/TNF-α secretion and elevation of immune checkpoint molecule expression, but did not affect perforin or granzyme B secretion. The current data indicated that IL-35 dampened the cytotoxicity of CD8 T cells in patients with IM probably via repression of cytokine secretion. Elevated IL-35 may protect against CD8 T cell-induced liver inflammation in patients with IM.
白细胞介素 (IL)-35 在传染病、自身免疫性疾病和癌症中发挥免疫抑制作用。然而，IL-35 在传染性单核细胞增多症 (IM) 中的表达及其对 CD8 T 细胞的调节作用尚未完全阐明。在这项研究中，我们比较了三组参与者，包括 23 例无肝炎症的 IM 患者、28 例有肝炎症的 IM 患者和 21 例对照者。分离血浆和外周血单个核细胞（PBMCs）。纯化 CD8 T 细胞。通过 ELISA 测定血浆 IL-35。体外用重组人 IL-35 刺激 PBMCs 和 CD8 T 细胞。通过 ELISPOT 评估穿孔素和颗粒酶 B 的分泌。通过流式细胞术研究免疫检查点分子的表达。CD8 T 细胞以直接接触和间接接触的方式与 HepG2 细胞共培养。通过测量乳酸脱氢酶释放和促炎细胞因子表达来计算 CD8 T 细胞的细胞毒性。无肝炎症的 IM 患者与对照者的血浆 IL-35 水平无显著差异，但伴有肝炎症的 IM 患者的 IL-35 水平显著升高，并与转氨酶呈负相关。伴有肝炎症的 IM 患者的 CD8 T 细胞显示出更强的细胞毒性。IL-35 刺激抑制了 IM 患者 CD8 T 细胞诱导的靶细胞死亡，主要通过抑制 IFN-γ/TNF-α 的分泌和上调免疫检查点分子的表达，但不影响穿孔素或颗粒酶 B 的分泌。这些数据表明，IL-35 通过抑制细胞因子分泌来抑制 IM 患者 CD8 T 细胞的细胞毒性。升高的 IL-35 可能在 IM 患者中通过抑制 CD8 T 细胞诱导的肝炎症来发挥保护作用。
