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

Molecular mechanisms that maintain lineage integrity of helper T cells are largely unknown. Here we show histone deacetylases (HDAC) 1 and 2 as crucial regulators of this process. Loss of HDAC1 and HDAC2 during late T cell development led to the appearance of MHC class II-selected CD4(+) helper T cells (T(H)) that expressed CD8 lineage genes such as Cd8a and Cd8b1. HDAC1-HDAC2-deficient T(H)0 and T(H)1 cells further up-regulated Cd8 lineage genes and acquired a CD8 effector program in a manner dependent on Runx-CBFβ complexes, while T(H)2 cells repressed CD8 lineage features independently of HDAC1 and HDAC2. These results demonstrate that HDAC1-HDAC2 maintain CD4 lineage integrity by repressing Runx-CBFβ complexes that otherwise induce a CD8-like effector program in CD4(+) T cells.