title: HDAC1 controls CD8+ T cell homeostasis and antiviral response.
abstract: 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/TCRβlo 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 IFNγ upon ex vivo PMA/ionomycin stimulation in comparison to wild-type cells. Naïve (CD44l°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.
authors.affiliation: Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Roland
authors.initials: R
authors.lastname: Tschismarov
authors.affiliation: Institute of Immunobiology, Cantonal Hospital St.Gallen, St. Gallen, Switzerland.
authors.forename: Sonja
authors.initials: S
authors.lastname: Firner
authors.affiliation: Institute of Immunobiology, Cantonal Hospital St.Gallen, St. Gallen, Switzerland.
authors.forename: Cristina
authors.initials: C
authors.lastname: Gil-Cruz
authors.affiliation: Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria; Division of Rheumatology, Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Lisa
authors.initials: L
authors.lastname: Göschl
authors.affiliation: Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Nicole
authors.initials: N
authors.lastname: Boucheron
authors.affiliation: Division of Rheumatology, Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Günter
authors.initials: G
authors.lastname: Steiner
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Novartis Research Foundation and University of Basel, Faculty of Sciences, Basel, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Matthias
authors.affiliation: Department of Medical Biochemistry, Max F. Perutz Laboratories, Vienna Biocenter, Medical University of Vienna, Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Seiser
authors.affiliation: Institute of Immunobiology, Cantonal Hospital St.Gallen, St. Gallen, Switzerland.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Ludewig
authors.affiliation: Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Ellmeier
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D056284:Histone Deacetylase 1 / Q000378:metabolism*; D018960:Hyaluronan Receptors / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D008216:Lymphocytic Choriomeningitis / Q000188:drug therapy / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D018960:Hyaluronan Receptors; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D015759:Ionomycin; D007371:Interferon-gamma; C484389:Hdac1 protein, mouse; D056284:Histone Deacetylase 1