Epigenetically Controlled ZEB2 Expression Promotes the Cytotoxic Potential of CMV-Specific CD8+ T Cells

Sasidharan Nair V, Yu Z, Ahmadi H, Bonifacius A, Pietzsch B, Busch DH, Cicin-Sain L, Müller F, Schober K, Eiz-Vesper B, Floess S, Huehn J (2025)

Publication Type: Journal article

Publication year: 2025

Journal

European Journal of Immunology Wiley-VCH Verlag

Book Volume: 55

Article Number: e70084

Journal Issue: 11

DOI: 10.1002/eji.70084

Abstract

Zinc finger E-box binding protein 2 (ZEB2) is a key factor in the differentiation of naïve CD8+ T cells into effector and memory T cells. However, the precise regulatory role of ZEB2 in cytotoxic CD8+ T cells remains unknown. Our recent DNA methylation analysis of cytomegalovirus (CMV)-specific human CD8+ T cells revealed two differentially methylated regions (DMRs) within the ZEB2 locus. In the present study, we show that these ZEB2 DMRs undergo pronounced demethylation during T cell differentiation. In particular, terminally differentiated CD8+ T cells and cytotoxic CD4+ T cells show an almost complete demethylation. Demethylation of the ZEB2 DMRs correlates strongly with ZEB2 expression in all T cell subsets. Furthermore, DNA methylation patterns remain stable during long-term in vitro culture. ZEB2 knockout in CD8+ effector T cells results in altered gene expression profiles, affecting genes related to cell–cell adhesion and impairing the cytotoxic capacity in CMV-specific killing assays. Our data show that ZEB2 expression contributes to the differentiation of naïve CD8+ T cells into effector and memory T cells and regulates the functional properties of virus-specific cytotoxic CD8+ T cells.

Authors with CRIS profile

Kilian Schober Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene

Involved external institutions

Helmholtz-Zentrum für Infektionsforschung (HZI) DE Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE) Technische Universität München (TUM) DE Germany (DE) Universität des Saarlandes (UdS) DE Germany (DE)

How to cite

APA:

Sasidharan Nair, V., Yu, Z., Ahmadi, H., Bonifacius, A., Pietzsch, B., Busch, D.H.,... Huehn, J. (2025). Epigenetically Controlled ZEB2 Expression Promotes the Cytotoxic Potential of CMV-Specific CD8+ T Cells. European Journal of Immunology, 55(11). https://doi.org/10.1002/eji.70084

MLA:

Sasidharan Nair, Varun, et al. "Epigenetically Controlled ZEB2 Expression Promotes the Cytotoxic Potential of CMV-Specific CD8+ T Cells." European Journal of Immunology 55.11 (2025).

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