Treatment of HIV-Infected Individuals with the Histone Deacetylase Inhibitor Panobinostat Results in Increased Numbers of Regulatory T Cells and Limits &ITEx Vivo&IT Lipopolysaccharide-Induced Inflammatory Responses
Christel Rothe Brinkmann, Jesper Falkesgaard Hojen, Thomas Aagaard Rasmussen, Anne Sofie Kjaer, Rikke Olesen, Paul W Denton, Lars Ostergaard, Zhengyu Ouyang, Mathias Lichterfeld, Xu Yu, Ole Schmeltz Sogaard, Charles Dinarello, Martin Tolstrup
mSphere | AMER SOC MICROBIOLOGY | Published : 2018
Histone deacetylase inhibitors (HDACi) modulate the transcriptional activity of all cells, including innate and adaptive immune cells. Therefore, we aimed to evaluate immunological effects of treatment with the HDACi panobinostat in HIV-infected patients during a clinical phase IIa latency reversal trial. Using flow cytometry, we investigated changes in T cell activation (CD69, CD38, HLA-DR) and the expression of CD39 and CTLA4 on regulatory T cells (Tregs). Whole-blood stimulations were performed and cytokine responses measured using Luminex. Gene expression in purified peripheral blood mononuclear cells (PBMCs) was evaluated using an Affymetrix HTA 2.0 gene chip. We found that proportions ..View full abstract
Awarded by NIH
Awarded by Danish Council for Strategic Research
Awarded by American Foundation for AIDS Research
The study was funded by the Danish Council for Strategic Research (grant 603-00521B to L.O.) and the American Foundation for AIDS Research (grant 108302-51-RGRL), by the Institute of Clinical Medicine at Aarhus University, and by NIH grant AI-15614 (to C.D.). Novartis provided panobinostat for the study. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.