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Proc Natl Acad Sci U S A. 2020 Mar 24;117(12):6686-6696. doi: 10.1073/pnas.1913940117. Epub 2020 Mar 11.

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

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Department of Hematopoiesis, Sanquin Research, 1066 CX Amsterdam, The Netherlands.
Landsteiner Laboratory, Oncode Institute, Amsterdam University Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Department of Research Facilities, Sanquin Research, 1066 CX Amsterdam, The Netherlands.
Division of Molecular Oncology and Immunology, Oncode Institute, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
Department of Molecular and Cellular Haemostasis, Sanquin Research, 1066 CX Amsterdam, The Netherlands.
Department of Hematopoiesis, Sanquin Research, 1066 CX Amsterdam, The Netherlands;


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.


CD29; IFN-γ; IL-2; T cells; cytotoxicity


Conflict of interest statement

The authors declare no competing interest.

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