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Nat Immunol. 2014 May;15(5):439-448. doi: 10.1038/ni.2864. Epub 2014 Mar 30.

CD4(+) T cell lineage integrity is controlled by the histone deacetylases HDAC1 and HDAC2.

Author information

Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, A-1090 Vienna, Austria.
Division of Rheumatology, Medicine III, Medical University of Vienna, 1090 Vienna, Austria.
Department of Medical Biochemistry, Max F. Perutz Laboratories, Vienna Biocenter, Medical University of Vienna, 1030 Vienna, Austria.
Division of Biosimulation and Bioinformatics, Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, 1090 Vienna, Austria.
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.
Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Laboratory for Transcriptional Regulation, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan.
Friedrich Miescher Institute for Biomedical Research, Novartis Research Foundation, 4058 Basel, Switzerland and University of Basel, Faculty of Sciences, 4051 Basel, Switzerland.
Contributed equally

Erratum in

  • Nat Immunol. 2014 Sep;15(9):894. Goeschl, Lisa [corrected to Göschl, Lisa].


Molecular mechanisms that maintain lineage integrity of helper T cells are largely unknown. Here we show histone deacetylases 1 and 2 (HDAC1 and HDAC2) as crucial regulators of this process. Loss of HDAC1 and HDAC2 during late T cell development led to the appearance of major histocompatibility complex (MHC) class II-selected CD4(+) helper T cells that expressed CD8-lineage genes such as Cd8a and Cd8b1. HDAC1 and HDAC2-deficient T helper type 0 (TH0) and TH1 cells further upregulated CD8-lineage genes and acquired a CD8(+) effector T cell program in a manner dependent on Runx-CBFβ complexes, whereas TH2 cells repressed features of the CD8(+) lineage independently of HDAC1 and HDAC2. These results demonstrate that HDAC1 and HDAC2 maintain integrity of the CD4 lineage by repressing Runx-CBFβ complexes that otherwise induce a CD8(+) effector T cell-like program in CD4(+) T cells.

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