白细胞介素-35可能通过抑制CD8+ T细胞功能在传染性单核细胞增多症诱导的肝脏炎症中发挥保护作用

IF 2.9 4区 医学 Q3 IMMUNOLOGY Archivum Immunologiae et Therapiae Experimentalis Pub Date : 2022-10-11 DOI:10.1007/s00005-022-00663-8
Ying Gao, Lan Li, Xingxing Hu, Weihua Zhang, Yu Li
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引用次数: 0

摘要

白细胞介素(IL)-35在感染性疾病、自身免疫性疾病和癌症中起免疫抑制作用。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细胞的调控尚不完全清楚。在本研究中,对三组参与者进行比较,包括23例无肝脏炎症的IM患者,28例肝脏炎症的IM患者和21例对照。分离血浆和外周血单核细胞(PBMCs)。纯化CD8+ T细胞。ELISA法检测血浆IL-35。重组人IL-35体外刺激PBMCs和CD8+ T细胞。elisa法检测穿孔素和颗粒酶B分泌情况。流式细胞术检测免疫检查点分子表达。CD8+ T细胞与HepG2细胞采用直接接触法和间接接触法共培养。通过乳酸脱氢酶的释放和促炎细胞因子的表达,计算CD8+ T细胞的细胞毒性。无肝脏炎症的IM患者血浆IL-35水平与对照组无显著差异,但有肝脏炎症的IM患者血浆IL-35水平明显升高,且与转氨酶呈负相关。IM合并肝炎症患者的CD8+ T细胞表现出更强的细胞毒性。IL-35刺激抑制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分泌和提高免疫检查点分子表达,但不影响穿孔素或颗粒酶B分泌。目前的数据表明,IL-35可能通过抑制细胞因子的分泌来抑制IM患者的CD8+ T细胞的细胞毒性。升高的IL-35可能对IM患者CD8+ T细胞诱导的肝脏炎症有保护作用。
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Interleukin-35 has a Protective Role in Infectious Mononucleosis-Induced Liver Inflammation Probably by Inhibiting CD8+ T Cell Function

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.

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来源期刊
CiteScore
5.90
自引率
0.00%
发文量
26
审稿时长
>12 weeks
期刊介绍: Archivum Immunologiae et Therapiae Experimentalis (AITE), founded in 1953 by Ludwik Hirszfeld, is a bimonthly, multidisciplinary journal. It publishes reviews and full original papers dealing with immunology, experimental therapy, immunogenetics, transplantation, microbiology, immunochemistry and ethics in science.
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