Distinction between antigen receptor and IL 2 receptor triggering events in the activation of alloreactive T cell clones with calcium ionophore and phorbol ester.
A previous study indicated that Ca++ ionophores in conjunction with the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) could induce normal T lymphocytes to express receptors for the T cell growth factor, interleukin 2 (IL 2), to secrete IL 2, and to proliferate (1). Here we used long-term alloreactive Lyt-2+ cytotoxic or T4+ "helper" T cell clones. In response to their specific alloantigen, all of the clones secreted IFN-gamma but only the T4+ clone secreted IL 2 and proliferated in response to the appropriate alloantigen in the absence of exogenous IL 2. The Ca++ ionophore ionomycin and TPA, used in conjunction, mimicked the effect of specific alloantigen on these T cell clones, i.e., they induced the secretion of IFN-gamma in all clones and the secretion of IL 2 in the T4+ clone. In the absence of exogenous IL 2, a proliferative response was induced only for the IL 2 secreting clone. Increased sensitivity to exogenous IL 2 for some T cell clones was also observed after either alloantigen or ionomycin and TPA treatment; this could be correlated with an increase in the expression of IL 2 receptors 6 hr after a pulse with ionomycin and TPA. These results suggest that, for a given T cell clone, activation of the Ca++ -dependent protein kinase c can replace the antigen-receptor triggering events leading to interleukin secretion and increased expression of IL 2 receptors but cannot substitute for the IL 2 dependent triggering of the IL 2 receptor.
D000818:Animals; D002999:Clone Cells / Q000276:immunology / Q000378:metabolism; D004357:Drug Synergism; D004987:Ethers / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D015759:Ionomycin; D007476:Ionophores / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008222:Lymphokines / Q000096:biosynthesis; D016215:Macrophage-Activating Factors; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D010704:Phorbols / Q000494:pharmacology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D011971:Receptors, Immunologic / Q000502:physiology*; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D004987:Ethers; D007376:Interleukin-2; D007476:Ionophores; D008222:Lymphokines; D016215:Macrophage-Activating Factors; D010704:Phorbols; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate