title: Modulation of human gamma/delta T-cell activation and phenotype by histone deacetylase inhibitors.
abstract: Histone deacetylase inhibitors have been shown to possess therapeutic potential in various pathophysiological conditions. Valproic acid (VPA), a known histone deacetylase class I inhibitor, has been studied for its influence on immune cell functions. However, the potential impact of VPA on human γδ T-cells remains unknown. Here we investigated the effects of VPA on the proliferation and the immunophenotype of human γδ T-cells. We observed dose-dependent inhibition of proliferation, associated with significant cell death as revealed by flow cytometry. The cellular response to VPA clearly showed differential modulation of cell surface markers on γδ T-cells when compared to αβ T-cells. Furthermore, histone H3 acetylation was detected in γδ T-cells even at toxic concentrations of VPA. Our investigations focusing on the impact of VPA on human γδ T-cells will be helpful in understanding its safety profile in clinical application, particularly in the context of γδ T-cell-targeted immunotherapy.
authors.affiliation: Institute of Immunology, Christian-Albrechts University, UKSH Campus Kiel, Arnold-Heller-Str. 3, Bldg. 17, D-24105 Kiel, Germany. Electronic address: jaydeep.bhat@uksh.de.
authors.forename: Jaydeep
authors.initials: J
authors.lastname: Bhat
authors.affiliation: Institute of Immunology, Christian-Albrechts University, UKSH Campus Kiel, Arnold-Heller-Str. 3, Bldg. 17, D-24105 Kiel, Germany. Electronic address: Hans-Heinrich.Oberg@uksh.de.
authors.forename: Hans-Heinrich
authors.initials: HH
authors.lastname: Oberg
authors.affiliation: Institute of Immunology, Christian-Albrechts University, UKSH Campus Kiel, Arnold-Heller-Str. 3, Bldg. 17, D-24105 Kiel, Germany. Electronic address: dietrich.kabelitz@uksh.de.
authors.forename: Dieter
authors.initials: D
authors.lastname: Kabelitz
mesh_terms: D000107:Acetylation; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D008213:Lymphocyte Activation / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D056572:Histone Deacetylase Inhibitors; D006657:Histones; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014635:Valproic Acid
keywords: Histone deacetylation inhibitor; Toxicity; Valproic acid; αβ T-cells; γδ T-cells