CD29 可鉴定具有增强细胞毒性潜力的 IFN-γ 产生的人 CD8 T 细胞。
CD29 identifies IFN-γ-producing human CD8 T cells with an increased cytotoxic potential.
机构信息
Department of Hematopoiesis, Sanquin Research, 1066 CX Amsterdam, The Netherlands.
Landsteiner Laboratory, Oncode Institute, Amsterdam University Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
出版信息
Proc Natl Acad Sci U S A. 2020 Mar 24;117(12):6686-6696. doi: 10.1073/pnas.1913940117. Epub 2020 Mar 11.
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.
细胞毒性 CD8 T 细胞可以通过产生细胞因子、趋化因子和颗粒酶来有效杀死靶细胞。然而，这些效应分子的表达具有高度的差异性，缺乏能够识别和预先选择具有细胞毒性表达谱的 CD8 T 细胞的工具。人 CD8 T 细胞可以分为产生 IFN-γ和 IL-2 的细胞。对产生细胞因子的固定 CD8 T 细胞进行的无偏转录组学和蛋白质组学分析表明，IL-2 细胞产生辅助细胞因子，而 IFN-γ 细胞产生细胞毒性分子。IFN-γ T 细胞在刺激前就已经表达表面标记 CD29。CD29 还标记了单细胞 RNA 测序数据中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，表明其具有稳定的表型。预先选择表达 CD29 的 MART1 TCR 工程 T 细胞增强了对靶细胞的杀伤能力。因此，我们提出 CD29 的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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