The inhibition of PI3K and Akt in human T cells selectively inhibits the proliferation of human Tregs compared with Tconvs in a dose-dependent manner.

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The inhibition of PI3K and Akt in human T cells selectively inhibits the proliferation of human Tregs compared with Tconvs in a dose-dependent manner. The inhibition of PI3K and Akt in human T cells selectively inhibits the proliferation of human Tregs compared with Tconvs in a dose-dependent manner. Tregs (CD4+CD25HI) and Tconvs (CD4+CD25−) were fractionated from human PBMCs by cell sorting. Proliferation was examined by dilution of CFSE after stimulation with anti-CD3/anti-CD28 for 3 days with titrated amounts of triciribine (TCN), MK-2206, wortmannin (WM), and IC87114. Dead cells were excluded by 7-AAD incorporation. Left, average of three experiments, normalized to untreated controls; right, representative examples. A, a significant reduction in Treg proliferation was observed in response to Akt inhibition by triciribine compared with that of Tconvs at all doses tested: 5 μmol/L (P = 0.04), 10 μmol/L (P = 0.03), and 50 μmol/L (P = 0.01). B, a significant reduction of Treg proliferation in response to MK-2206 treatment was observed compared with that of Tconvs at the 1 μmol/L (P = 0.05) and 5 μmol/L (P = 0.005) doses. C, proliferation of Tregs was significantly reduced by wortmannin compared with that of Tconvs at all doses tested: 300 nmol/L (P = 0.03), 800 nmol/L (P = 0.01), and 1,000 nmol/L (P = 0.002). D, Treg proliferation was significantly reduced by IC87114 compared with that of Tconvs at the 10 μmol/L (P = 0.04) and 20 μmol/L (P < 0.005) doses. *, P < 0.05. Rasha Abu-Eid et al. Cancer Immunol Res 2014;2:1080-1089 ©2014 by American Association for Cancer Research