PT  - JOURNAL ARTICLE
AU  - Benoît P. Nicolet
AU  - Aurélie Guislain
AU  - Floris P.J. van Alphen
AU  - Raquel Gomez-Eerland
AU  - Ton N. M. Schumacher
AU  - Maartje van den Biggelaar
AU  - Monika C. Wolkers
TI  - CD29 marks superior cytotoxic human CD8<sup>+</sup> T cells
AID  - 10.1101/562512
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 562512
4099  - http://biorxiv.org/content/early/2019/08/09/562512.short
4100  - http://biorxiv.org/content/early/2019/08/09/562512.full
AB  - 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 pre-select potent killer cells 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 could be identified with 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, the cytotoxic features of CD29+ T cells were maintained during cell culture, suggesting a stable phenotype. Pre-selecting 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.