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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.

Author information

1
Department of Hematopoiesis, Sanquin Research, 1066 CX Amsterdam, The Netherlands.
2
Landsteiner Laboratory, Oncode Institute, Amsterdam University Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
3
Department of Research Facilities, Sanquin Research, 1066 CX Amsterdam, The Netherlands.
4
Division of Molecular Oncology and Immunology, Oncode Institute, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
5
Department of Molecular and Cellular Haemostasis, Sanquin Research, 1066 CX Amsterdam, The Netherlands.
6
Department of Hematopoiesis, Sanquin Research, 1066 CX Amsterdam, The Netherlands; m.wolkers@sanquin.nl.

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.

KEYWORDS:

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

PMID:
32161126
DOI:
10.1073/pnas.1913940117

Conflict of interest statement

The authors declare no competing interest.

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