CD4(+) T cell lineage integrity is controlled by the histone deacetylases HDAC1 and HDAC2
Résumé
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-CBFbeta 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-CBFbeta complexes that otherwise induce a CD8(+) effector T cell-like program in CD4(+) T cells.
Mots clés
Animals
Mice
Inbred C57BL
Knockout
Protein Binding
Cells
Cultured
Cytokines/metabolism
CD4-Positive T-Lymphocytes/*immunology
CD8-Positive T-Lymphocytes/*immunology
Cell Differentiation/genetics
Cell Lineage/genetics
Core Binding Factor alpha Subunits/metabolism
Core Binding Factor beta Subunit/metabolism
Cytotoxicity
Immunologic/genetics
Histocompatibility Antigens Class II/genetics/metabolism
Histone Deacetylase 1/genetics/*metabolism
Histone Deacetylase 2/genetics/*metabolism
Th1 Cells/*immunology