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白细胞介素-15与RAE-1ɛ协同作用,刺激CD8(+) T细胞的非T细胞受体依赖性增殖和活化。

IL-15, in synergy with RAE-1ɛ, stimulates TCR-independent proliferation and activation of CD8(+) T cells.

作者信息

Qian Li, Zhang Yue, Pan Xin-Yuan, Ji Ming-Chun, Gong Wei-Juan, Tian Fang

机构信息

Department of Immunology, School of Medicine, Yangzhou University, Yangzhou 225001.

出版信息

Oncol Lett. 2012 Feb;3(2):472-476. doi: 10.3892/ol.2011.495. Epub 2011 Nov 25.

Abstract

CD8(+) T cells play critical roles in immunosurveillance by killing malignant or virally infected cells. Interleukin 15 (IL-15) is a critical cytokine for promoting proliferation and the effector capacity of CD8(+) T cells, and has been used to support the growth of CD8(+) T cells in cellular therapies of neoplastic diseases. Recent studies have shown that IL-15, in synergy with other cytokines, such as IL-6, enhances the T-cell receptor (TCR)-independent proliferation and function of CD8(+) T cells. The aim of the present study was to investigate the role of BaF3-mb15-RAE cells in stimulating mouse CD8(+) T cells. BaF3 cells were cultured and B16F10 cells were grown in DMEM. MTT assay was used to detect the proliferation of CD8(+) T cells. Cells were analyzed using flow cytometry. The results showed that IL-15 synergistically acts with another T-cell stimulatory molecule, RAE1ɛ, to potently promote the proliferation of CD8(+) T cells, induce CD8(+) T-cell activation and enhance granzyme B and interferon-γ (IFN-γ) production in the absence of signaling via the TCR. Moreover, IL-15 in combination with RAE1ɛ resulted in a cooperative effect on CD8(+) T-cell-mediated cytotoxicity against B16F10 tumor cells. Thus, results of the present study showed that IL-15, in synergy with RAE1ɛ, enhances the TCR-independent effector function of CD8(+) T cells in vitro, which may be useful in the cellular immunotherapy of cancer.

摘要

CD8(+) T细胞通过杀伤恶性或病毒感染细胞在免疫监视中发挥关键作用。白细胞介素15(IL-15)是促进CD8(+) T细胞增殖和效应能力的关键细胞因子,已被用于支持肿瘤疾病细胞治疗中CD8(+) T细胞的生长。最近的研究表明,IL-15与其他细胞因子(如IL-6)协同作用,可增强CD8(+) T细胞不依赖T细胞受体(TCR)的增殖和功能。本研究的目的是探讨BaF3-mb15-RAE细胞在刺激小鼠CD8(+) T细胞中的作用。将BaF3细胞进行培养,B16F10细胞在DMEM中生长。采用MTT法检测CD8(+) T细胞的增殖。使用流式细胞术对细胞进行分析。结果表明,IL-15与另一种T细胞刺激分子RAE1ɛ协同作用,在不通过TCR信号传导的情况下,有力地促进CD8(+) T细胞的增殖,诱导CD8(+) T细胞活化,并增强颗粒酶B和干扰素-γ(IFN-γ)的产生。此外,IL-15与RAE1ɛ联合对CD8(+) T细胞介导的针对B16F10肿瘤细胞的细胞毒性产生协同作用。因此,本研究结果表明,IL-15与RAE1ɛ协同作用可增强体外CD8(+) T细胞不依赖TCR的效应功能,这可能在癌症的细胞免疫治疗中有用。

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