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.
D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D018801:CD2 Antigens; D017252:CD3 Complex; D002455:Cell Division / Q000187:drug effects; D004075:Diglycerides / Q000502:physiology*; D004533:Egtazic Acid / Q000494:pharmacology; D004987:Ethers / Q000494:pharmacology; D005989:Glycerides / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000502:physiology; D015759:Ionomycin; D008213:Lymphocyte Activation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D011971:Receptors, Immunologic / Q000502:physiology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D017252:CD3 Complex; D004075:Diglycerides; D004987:Ethers; D005989:Glycerides; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; C044295:1,2-dioctanoylglycerol; D004533:Egtazic Acid; D015759:Ionomycin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate