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

Abstract

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 (T H 0) and T H 1 cells further upregulated CD8-lineage genes and acquired a CD8 + effector T cell program in a manner dependent on Runx-CBFβ complexes, whereas T H 2 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. © 2014 Nature America, Inc.