| First Author | Tschismarov R | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 10 | Pages | e110576 |
| PubMed ID | 25333902 | Mgi Jnum | J:223548 |
| Mgi Id | MGI:5649487 | Doi | 10.1371/journal.pone.0110576 |
| Citation | Tschismarov R, et al. (2014) HDAC1 controls CD8+ T cell homeostasis and antiviral response. PLoS One 9(10):e110576 |
| abstractText | 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/TCRbetalo population, indicating that HDAC1 is essential for the efficient progression of immature CD8+CD4- cells to the DP stage. Moreover, CD44hi effector CD8+ T cells were enhanced in mice with a T cell-specific deletion of HDAC1 under homeostatic conditions and HDAC1-deficient CD44hi CD8+ T cells produced more IFNgamma upon ex vivo PMA/ionomycin stimulation in comparison to wild-type cells. Naive (CD44l degrees CD62L+) HDAC1-null CD8+ T cells displayed a normal proliferative response, produced similar amounts of IL-2 and TNFalpha, slightly enhanced amounts of IFNgamma, 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. |
