CD29 identifies IFN-γ-producing human CD8⁺ T cells with an increased cytotoxic potential

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.