期刊名称:Proceedings of the National Academy of Sciences
印刷版ISSN:0027-8424
电子版ISSN:1091-6490
出版年度:2020
卷号:117
期号:12
页码:6686-6696
DOI:10.1073/pnas.1913940117
出版社:The National Academy of Sciences of the United States of America
摘要: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.