CD29 marks superior cytotoxic human T cells

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 pre-select potent killer cells are lacking. Human CD8 + T cells can be divided into IFN-γ and IL-2 producing cells. Unbiased RNA-sequencing and proteomics analysis on cytokine-producing fixed cells revealed that IL-2 + T cells produce helper cytokines, and that IFN-γ + T 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 selecting for CD29 + T cells could boost the anti-tumoral activity of T cell therapeutics.