Granulocyte colony-stimulating factor impairs CD8+ T cell functionality by interfering with central activation elements
Granulocyte colony-stimulating factor impairs CD8+ T cell functionality by interfering with central activation elements
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DOI：
10.1111/cei.12794
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发表时间：
2016-07-01
影响因子：
4.6
通讯作者：
Eiz-Vesper, B.
中科院分区：
文献类型：
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作者：
Bunse, C. E.;Tischer, S.;Eiz-Vesper, B.
除了将干细胞动员到外周之外，粒细胞集落刺激因子（G-CSF）已被证明可以影响各种类型的先天性和适应性免疫细胞。例如，它会损害细胞毒性 T 淋巴细胞 (CTL) 的效应功能。据推测，这种效应是由受 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，分离的G-CSF处理的CD8+T细胞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）进行抗原依赖性刺激，或用抗CD3/CD28刺激珠进行抗原独立刺激。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，我们首次证明G-CSF对CD8（+）CTL具有直接作用，这是基于细胞毒性T细胞系TALL-104在G-CSF处理后IFN-和颗粒酶B的产生减少而得到证实的。通过进一步研究干细胞供体和未处理对照的 CTL 中受 G-CSF 影响的元素，我们发现 G-CSF 处理后细胞外调节激酶 (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。此外，miRNA-155 和激活标记物的表达水平也有所降低。总之，我们的结果表明，G-CSF直接影响细胞毒性CD8(+) T细胞的效应功能，并影响T细胞活化的各个元件。
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.