Fig. 4

Inhibition of p300/CBP histone acetyltransferases reduced effector cytokine production and prevented terminal differentiation. PBMCs were stimulated with anti-CD3/CD28 mAbs plus rhIL-2 (200 IU/mL) for 48 h, with or without C646 (5 µM). a Brefeldin A was added during the last 4 h of stimulation; production of IFN-γ⁺ and TNF-α⁺ in C646-treated or untreated CD8⁺ T cells was measured by ICS. b IFN-γ⁺ and TNF-α concentrations in culture supernatants of PBMCs that were treated with/without C646 were detected by ELISA. c acH3 abundance at the promoter region of IFNG and TNF loci in C646-treated or untreated CD8⁺ T cells was assessed by ChIP. d mRNA expressions of IFNG, GZMB, PRF1, TCF7 and TOX in C646-treated or untreated CD8⁺ T cells as determined by quantitative PCR, data were normalized to C646 untreated group. e & f Expression of KLRG1 (e) and CD127 (f) with/without C646 treatment, representative histograms (left) and summary results of gMFI (right) were shown. g Representative dot-plots of T cell subset compositions (left), and statistical presentation of individual T cell subsets between C646-treated and non-treated CD8⁺ T cells after 8-day expansion (right). All experiments were repeated three to five independent times with 1–3 individuals each time