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CD29 identifies IFN-γ-producing human CD8+ T cells with an increased cytotoxic potential.
CD29 鉴定产生IFN-γ 的人CD8 + T细胞,细胞毒潜能增加。
- 影响因子:8.58
- DOI:10.1073/pnas.1913940117
- 作者列表:"Nicolet BP","Guislain A","van Alphen FPJ","Gomez-Eerland R","Schumacher TNM","van den Biggelaar M","Wolkers MC
- 发表时间:2020-03-24
Abstract
:Cytotoxic CD8+ T cells can effectively kill target cells by producing cytokines, chemokines, and granzymes. Expression of these effector molecules is however highly divergent, and tools that identify and preselect CD8+ T cells with a cytotoxic expression profile are lacking. Human CD8+ T cells can be divided into IFN-γ- and IL-2-producing cells. Unbiased transcriptomics and proteomics analysis on cytokine-producing fixed CD8+ T cells revealed that IL-2+ cells produce helper cytokines, and that IFN-γ+ cells produce cytotoxic molecules. IFN-γ+ T cells expressed the surface marker CD29 already prior to stimulation. CD29 also marked T cells with cytotoxic gene expression from different tissues in single-cell RNA-sequencing data. Notably, CD29+ T cells maintained the cytotoxic phenotype during cell culture, suggesting a stable phenotype. Preselecting CD29-expressing MART1 TCR-engineered T cells potentiated the killing of target cells. We therefore propose that CD29 expression can help evaluate and select for potent therapeutic T cell products.
摘要
: 细胞毒性CD8 + T细胞可通过产生细胞因子、趋化因子和颗粒酶有效杀伤靶细胞。然而,这些效应分子的表达高度分化,缺乏识别和预选具有细胞毒性表达谱的CD8 + T细胞的工具。人CD8 + T细胞可分为IFN-γ-和IL-2-producing细胞。对产生细胞因子的固定CD8 + T细胞进行无偏转录组学和蛋白质组学分析,发现IL-2 + 细胞产生辅助细胞因子,IFN-γ + 细胞产生细胞毒性分子。IFN-γ + T细胞在刺激前已经表达了表面标志物CD29。在单细胞RNA测序数据中,CD29 还标记了来自不同组织的具有细胞毒性基因表达的T细胞。值得注意的是,CD29 + T细胞在细胞培养过程中保持细胞毒性表型,提示表型稳定。预选CD29-expressing的MART1 TCR工程T细胞增强了对靶细胞的杀伤作用。因此,我们提出CD29 表达可以帮助评估和选择有效的治疗性T细胞产品。
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