HDAC1 Controls CD8(+) T Cell Homeostasis and Antiviral Response

Reversible lysine acetylation plays an important role in the regulation of T cell responses. HDAC1 has been shown to control peripheral T helper cells, however the role of HDAC1 in CD8(+) T cell function remains elusive. By using conditional gene targeting approaches, we show that LckCre-mediated deletion of HDAC1 led to reduced numbers of thymocytes as well as peripheral T cells, and to an increased fraction of CD8(+)CD4(–) cells within the CD3/TCRβ(lo) population, indicating that HDAC1 is essential for the efficient progression of immature CD8(+)CD4(–) cells to the DP stage. Moreover, CD44(hi) effector CD8(+) T cells were enhanced in mice with a T cell-specific deletion of HDAC1 under homeostatic conditions and HDAC1-deficient CD44(hi) CD8(+) T cells produced more IFNγ upon ex vivo PMA/ionomycin stimulation in comparison to wild-type cells. Naïve (CD44(l)°CD62L(+)) HDAC1-null CD8(+) T cells displayed a normal proliferative response, produced similar amounts of IL-2 and TNFα, slightly enhanced amounts of IFNγ, and their in vivo cytotoxicity was normal in the absence of HDAC1. However, T cell-specific loss of HDAC1 led to a reduced anti-viral CD8(+) T cell response upon LCMV infection and impaired expansion of virus-specific CD8(+) T cells. Taken together, our data indicate that HDAC1 is required for the efficient generation of thymocytes and peripheral T cells, for proper CD8(+) T cell homeostasis and for an efficient in vivo expansion and activation of CD8(+) T cells in response to LCMV infection.