Activation of human T cells with the physiological regulator of protein kinase C

We investigated whether sn-1,2-dioctanoylglycerol (diC8) activates highly purified human T cells. diC8's signaling activity was also compared with that of 12-O-tetradecanoylphorbol-13-acetate (TPA). diC8 and ionomycin were synergistic in promoting T-cell proliferation. The proliferative response was dependent upon an operational interleukin-2 (IL-2) system and exhibited a high degree of specificity; sn-1,2-diC8 was twice as active as racemic-1,2-diC8, and diC8 and TPA were not synergistic. diC8's signaling activity differed from that of TPA. diC8, unlike TPA, failed to elicit IL-2 receptors or proliferation, independently of ionomycin. diC8 also failed to promote the proliferation of T cells signaled with anti-CD3 or -CD2 monoclonal antibodies. Two different inhibitors of PKC, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine or staurosporine, inhibited T-cell proliferation induced with diC8 and ionomycin, but not with TPA and ionomycin. These observations, in addition to demonstrating the differential activity of diC8 and TPA, document a signaling role for diacylglycerol in the activation of normal T cells.