Characterization of the role for calcium influx in mitogen-induced triggering of human T cells. Identification of calcium-dependent and calcium-independent signals.
Entry of Ca2+ into the cell is recognized as an important activation signal for mitogen-induced lymphocyte proliferation. Changes in free cytosolic Ca2+ [( Ca2+]i) can now be measured directly using the fluorescent reagent quin-2. To analyze the role of [Ca2+]i in human T cell activation, we have determined the effect of the calcium channel blocker, nifedipine, on phytohemagglutinin (PHA)-induced lymphocyte proliferation. At a concentration of 50 microM, nifedipine is nontoxic, and prevents PHA-induced proliferation. In parallel the drug prevents the lectin-induced increase in concentration of [Ca2+]i and interleukin 2 (IL2) secretion; IL2 receptor expression is unaffected. In the presence of exogenous IL2, cell proliferation proceeds normally. Treatment of the cells with the tumor promoter 12-O-tetradecanoylphorbol 13-acetate prevents the inhibitory effect of nifedipine on cell proliferation. Since TPA is itself nonmitogenic and does not affect levels of cytosolic Ca2+, these data and the data on IL2 receptor expression indicate that PHA can generate an activation signal(s) which is [Ca2+]i independent.
D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000502:physiology; D011971:Receptors, Immunologic / Q000032:analysis; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007376:Interleukin-2; D010835:Phytohemagglutinins; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D009543:Nifedipine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium