MEK inhibition decreases mTOR activity in T cells.

<p>Splenocytes from B6 mice were pretreated or not for one hour with 10 µM UO126 and cultured for 2 to 48 hrs with or without anti-CD3 + anti-CD28 stimulation (5 µg/mL each). Phosphorylation of ERK (A, B), T421/S424-S6K (C, D) and T389-S6K (E, F) in CD8+ T cells was measured by flow cytometry. A, C, E: Representative histograms of unstimulated cells (filled histogram), cells stimulated with CD3+CD28 and treated (red line) or not (black line) with UO126, gated on CD8+ T cells. Graphs are representative of 3 to 5 experiments. C, D, F: Fold increase phosphorylation of ERK, T421/S424-S6K and T389-S6K in anti-CD3 + anti-CD28 stimulated CD8+ T cells treated (red) or not (black) with UO126, compared to unstimulated cells. Each dot represents an independent experiment. p-ERK, p-T421/S424-S6K and p-T389-S6K levels were normalized within each experiment to unstimulated control T cells. *: p<0.05, paired t-test.