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 mitogeninduced 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 μM, 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.