CD29 identifies IFN-γ–producing human CD8+ T cells with an increased cytotoxic potential
Benoît P. Nicolet, Aurélie Guislain, Floris P. J. van Alphen, Raquel Gomez-Eerland, Ton N. M. Schumacher, Maartje van den Biggelaar, and Monika C. Wolkers
PNAS March 24, 2020 117 (12) 6686-6696; first published March 11, 2020 https://doi.org/10.1073/pnas.1913940117
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Edited by Anjana Rao, La Jolla Institute for Allergy and Immunology, La Jolla, CA, and approved February 12, 2020 (received for review August 12, 2019)
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Significance
Human CD8+ T cells can effectively kill target cells. However, not all CD8+ T cells are equally efficient herein. We developed a method to dissect the transcriptome and proteome of FACS-sorted cytokine-producing fixed human CD8+ T cells. We show that CD29 identifies IFN-γ–producing CD8+ T cells with high expression levels of cytotoxic molecules. Preselecting for CD29+ T cells potentiated the killing capacity of CD8+ T cell products. Reanalysis of published scRNA-seq data revealed a core signature of CD29+ T cells, which had a good predictive value for survival in melanoma patients. In conclusion, our study provides fundamental insights in the heterogeneity and functionality of human CD8+ T cells, which could help potentiate the efficacy of adoptive T cell therapies.
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.作者: StephenW 时间: 2020-3-25 12:00
CD29鉴定具有增加的细胞毒性潜能的产生IFN-γ的人CD8 + T细胞
BenoîtP. Nicolet，AurélieGuislain，Floris P.J. van Alphen，Raquel Gomez-Eerland，Ton N.M.Schumacher，Maartje van den Biggelaar和Monika C.Wolkers
PNAS 2020年3月24日117（12）6686-6696;首次发布于2020年3月11日https://doi.org/10.1073/pnas.1913940117
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