Bhat Jaydeep, Oberg Hans-Heinrich, Kabelitz Dieter
Institute of Immunology, Christian-Albrechts University, UKSH Campus Kiel, Arnold-Heller-Str. 3, Bldg. 17, D-24105 Kiel, Germany.
Cell Immunol. 2015 Jul;296(1):50-6. doi: 10.1016/j.cellimm.2015.01.019. Epub 2015 Feb 14.
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.
组蛋白去乙酰化酶抑制剂已被证明在各种病理生理条件下具有治疗潜力。丙戊酸（VPA）是一种已知的I类组蛋白去乙酰化酶抑制剂，其对免疫细胞功能的影响已得到研究。然而，VPA对人γδ T细胞的潜在影响仍然未知。在此，我们研究了VPA对人γδ T细胞增殖和免疫表型的影响。我们观察到增殖受到剂量依赖性抑制，流式细胞术显示这与显著的细胞死亡有关。与αβ T细胞相比，γδ T细胞对VPA的细胞反应明显显示出细胞表面标志物的差异调节。此外，即使在VPA的毒性浓度下，γδ T细胞中也检测到组蛋白H3乙酰化。我们对VPA对人γδ T细胞影响的研究将有助于了解其在临床应用中的安全性，特别是在γδ T细胞靶向免疫治疗的背景下。
