Figure 2. JQI, a BET bromodomain inhibitor, maintains CD8⁺ T cells with features of stem cell–like and central memory T cells.

(A) Frequency of CD45RA^+/–CD62L⁺CCR7⁺ cells within the CD8⁺ T cell population cultured for 14 days in the presence of JQ1 or (–)-JQ1 (n = 7, paired t test). (B) Expression of CD27, CD28, CD127, and CD95 in the CD8⁺ T cells cultured in the presence of JQ1 or (–)-JQ1. Representative FACS plots of the samples shown in A. (C and D) CD45RA⁺CD62L⁺CCR7⁺ T cells were stimulated weekly with aAPC/mOKT3 and cultured with or without JQ1. Representative FACS plots of CD45RA, CD62L, and CCR7 expression at the indicated time points (C) as well as the frequency of CD45RA^+/–CD62L⁺CCR7⁺ cells within the CD8⁺ T cell population 21 days following initial stimulation (D) are shown (n = 5, paired t test). (E and F) The secretion of IL-2, IFN-γ, and TNF-α was evaluated by intracellular flow cytometry in CD8⁺CD45RA⁺CD62L⁺CCR7⁺ T cells cultured for 14 days with or without JQ1. The frequency of each cytokine-producing cell type (E) and those secreting all 3 cytokines (F) are shown (n = 5, paired t test). (G) Expression profiles of representative genes with differential expression between the T_SCM/T_CM and T_EM phenotypes. Fold expression levels in JQ1-treated CD8⁺ T cells relative to those in the control T cells are shown (n = 4). Error bars indicate the SD. (H) CD3⁺ T cells isolated from HLA-A2⁺ donors were stimulated by artificial antigen-presenting cells that express HLA-A*02:01, CD80, and CD83 (aAPC/A2) and were pulsed with the MART1_27–35 peptide once per week. The frequency of CD45RA^+/–CD62L⁺CCR7⁺ cells within the A2/MART1 multimer⁺ CD8⁺ T cell population 21 days after initial stimulation is shown (n = 4, paired t test). NS, not significant.