白介素15上调CD4 +和CD8 + T细胞上PD-1和TIM-3的表达

StephenW

Interleukin 15 upregulates the expression of PD-1 and TIM-3 on CD4 + and CD8 + T cells
Mohamad S Hakim  1   2 , Rizka O A Jariah  3 , Michelle Spaan  4 , Andre Boonstra  4
Affiliations
Affiliations

    1
    Department of Microbiology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada Yogyakarta, Indonesia.
    2
    Postgraduate School of Molecular Medicine, Erasmus MC-University Medical Center Rotterdam The Netherlands.
    3
    Department of Health Science, Faculty of Vocational Studies, Universitas Airlangga Surabaya, Indonesia.
    4
    Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center Rotterdam The Netherlands.

    PMID: 32704430 PMCID: PMC7364376

Abstract

Virus-specific T cell-mediated immunity is severely impaired in chronic hepatitis B virus (HBV) patients. HBV-specific T cells in chronic HBV patients show a low ability to produce cytokines and to exert their cytotoxic activity. A prominent characteristic of these exhausted T cells is overexpression of inhibitory receptor molecules which negatively regulate T cell function. In this study, we examined in vitro regulation of two inhibitory receptor expressions, programmed death 1 (PD-1) and T cell immunoglobulin mucin domain-containing molecule 3 (TIM-3). Peripheral blood mononuclear cells (PBMCs) obtained from healthy individuals were in vitro stimulated with a panel of cytokines. PD-1 and TIM-3 expression levels on CD4+ and CD8+ T cells were examined at days 2 and 7 post stimulation. We demonstrated that PD-1 and TIM-3 were induced via polyclonal (anti-CD3) and cytokine (interleukin 15 [IL-15]) stimulations. Noteworthy, there was a significantly increased induction of TIM-3 on CD8+ T cells as compared to CD4+ T cells. Our study thus contributes to further understanding the regulation of T cell exhaustion markers PD-1 and TIM-3.

Keywords: Inhibitory receptors; PD-1; T cells; TIM-3; interleukin 15.

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StephenW

白介素15上调CD4 +和CD8 + T细胞上PD-1和TIM-3的表达
Mohamad S Hakim 1 2，Rizka O A Jariah 3，Michelle Spaan 4，Andre Boonstra 4
隶属关系
隶属关系

    1个
    印度尼西亚日惹大学马达加斯加大学医学院公共卫生与护理学院微生物学系。
    2
    荷兰鹿特丹伊拉斯姆斯MC大学医学中心分子医学研究生院。
    3
    印度尼西亚泗水艾尔朗加大学职业学院卫生科学系。
    4
    荷兰鹿特丹伊拉斯姆斯大学医学中心胃肠病学和肝病学系。

    PMID：32704430 PMCID：PMC7364376

抽象

在慢性乙型肝炎病毒（HBV）患者中，病毒特异性T细胞介导的免疫力严重受损。慢性HBV患者的HBV特异性T细胞显示出低的产生细胞因子和发挥其细胞毒活性的能力。这些耗尽的T细胞的突出特征是抑制性调节T细胞功能的受体分子的过表达。在这项研究中，我们检查了两种抑制性受体表达的体外调控，即程序性死亡1（PD-1）和含T细胞免疫球蛋白粘蛋白结构域的分子3（TIM-3）。用一组细胞因子体外刺激获自健康个体的外周血单核细胞（PBMC）。在刺激后第2天和第7天检查CD4 +和CD8 + T细胞上PD-1和TIM-3的表达水平。我们证明PD-​​1和TIM-3是通过多克隆（抗CD3）和细胞因子（白介素15 [IL-15]）刺激诱导的。值得注意的是，与CD4 + T细胞相比，TIM-3对CD8 + T细胞的诱导显着增加。因此，我们的研究有助于进一步了解T细胞衰竭标志物PD-1和TIM-3的调控。

关键词：抑制性受体PD-1； T细胞； TIM-3;白介素15。

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