Fig. 3.

Ado/A2AR signaling modulates PKA and mTORC1 activation and impairs CD8⁺ T cell metabolic fitness and cytokine production. a Cumulative data of p-CREB expression in CD8⁺ T cells treated with the indicated combinations of Ado, A2AR agonist (CGS 21680), A2AR/A2BR antagonists (ZM 241385 and PSB 1115, respectively) and the PKA inhibitor KT570 (n = 7). b Cumulative data of p-S6 expression in CD8⁺ T cells treated with the indicated combinations of Ado, A2AR agonist (CGS 21680), A2AR/A2BR antagonists (ZM 241385 and PSB 1115, respectively), the PKA inhibitor KT570 or the mTOR inhibitor rapamycin (RAPA) and stimulated for 3 h by anti-CD3/anti-CD28-coated beads. c Representative example of 3 independent experiments depicting the OXPHOS (measured as the oxygen consumption rate; OCR) and the glycolytic (measured as the extracellular acidification rate; ECAR) metabolism in CD8⁺ T cells stimulated overnight by anti-CD3/CD28-coated beads in the presence of the indicated combinations of Ado and the A2AR antagonist ZM 241385. d Cumulative data of CD71 and CD98 expression or 2-NBDG uptake in CD8⁺ T cells treated with the indicated combinations of Ado and A2AR/A2BR antagonists (ZM 241385 and PSB 1115, respectively) or the PKA inhibitor KT570 and stimulated overnight by anti-CD3/anti-CD28-coated beads (n = 6, n = 7 and n = 8 from left to right). e Cumulative data of the fold reduction in CD8⁺ T cell IFN-γ production after treatment with combinations of Ado and A2AR antagonist (ZM 241385) or the PKA inhibitor KT570 and stimulated overnight by anti-CD3/anti-CD28-coated beads (n = 5). In all box charts, the 25th to 75th percentiles, the median and min-max of the values are presented; *P < 0.05, **P < 0.01, ***P < 0.001. Wilcoxon and/or one-way ANOVA tests