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首页> 外文期刊>Clinical and Experimental Immunology: An Official Journal of the British Society for Immunology >Granulocyte colony-stimulating factor impairs CD8(+) T cell functionality by interfering with central activation elements
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Granulocyte colony-stimulating factor impairs CD8(+) T cell functionality by interfering with central activation elements

机译：粒细胞集落刺激因子通过干扰中央激活元件来损害CD8（+）T细胞功能。

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摘要

Besides mobilizing stem cells into the periphery, granulocyte colony-stimulating factor (G-CSF) has been shown to influence various types of innate and adaptive immune cells. For example, it impairs the effector function of cytotoxic T lymphocytes (CTLs). It is assumed that this effect is mediated indirectly by monocytes, regulatory T cells and immunomodulatory cytokines influenced by G-CSF. In this study, isolated G-CSF-treated CD8(+) T cells were stimulated antigen-dependently with peptide-major histocompatibility complex (pMHC)-coupled artificial antigen-presenting cells (aAPCs) or stimulated antigen-independently with anti-CD3/CD28 stimulator beads. By measuring the changes in interferon (IFN)- and granzyme B expression at the mRNA and protein level, we showed for the first time that G-CSF has a direct effect on CD8(+) CTLs, which was confirmed based on the reduced production of IFN- and granzyme B by the cytotoxic T cell line TALL-104 after G-CSF treatment. By investigating further elements affected by G-CSF in CTLs from stem cell donors and untreated controls, we found a decreased phosphorylation of extracellular-regulated kinase (ERK)1/2, lymphocyte-specific protein tyrosine kinase (Lck) and CD3 after G-CSF treatment. Additionally, miRNA-155 and activation marker expression levels were reduced. In summary, our results show that G-CSF directly influences the effector function of cytotoxic CD8(+) T cells and affects various elements of T cell activation.
机译：除了动员干细胞进入外周，粒细胞集落刺激因子（G-CSF）已显示会影响各种类型的先天和适应性免疫细胞。例如，它损害细胞毒性T淋巴细胞（CTL）的效应子功能。假定这种作用是由受G-CSF影响的单核细胞，调节性T细胞和免疫调节细胞因子间接介导的。在这项研究中，用肽-主要组织相容性复合物（pMHC）偶联的人工抗原呈递细胞（aAPC）抗原依赖性地刺激了分离的G-CSF处理过的CD8（+）T细胞，或者用抗CD3 / CD28刺激珠。通过测量mRNA和蛋白水平上干扰素（IFN）-和颗粒酶B表达的变化，我们首次表明G-CSF对CD8（+）CTL有直接影响，这是基于产量减少所证实的G-CSF处理后，细胞毒性T细胞系TALL-104对IFN-和颗粒酶B的抑制作用。通过调查来自干细胞供体和未经治疗的对照的CTL中受G-CSF影响的其他元素，我们发现G-后G-CSF的胞外调节激酶（ERK）1/2，淋巴细胞特异性蛋白酪氨酸激酶（Lck）和CD3的磷酸化降低脑脊液治疗。另外，miRNA-155和激活标志物表达水平降低。总之，我们的结果表明，G-CSF直接影响细胞毒性CD8（+）T细胞的效应子功能，并影响T细胞活化的各种元素。

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