Increase in cytosolic free calcium concentration is an intracellular messenger for the production of interleukin 2 but not for expression of the interleukin 2 receptor

Abstract

Activation of lymphocytes by mitogenic lectins results in the production of a group of soluble factors, the lymphokines. Proliferation of activated T cells requires interaction of one of these lymphokines, interleukin 2 (IL 2), with its receptor. The induction of IL 2 receptor expression and IL 2 production may involve different activation signals; some mitogens or antigens may activate both, whereas others may activate only one. An increase in cytosolic free calcium concentrations [( Ca++]i) is one of the signals involved in cellular activation by lectins. By using the fluorescent indicator quin-2, we have demonstrated that increases in [Ca++]i accompany phytohemagglutinin induced proliferative responses of human T lymphocytes. Preventing the increase in [Ca++]i also prevents proliferation. We demonstrate that an increase in [Ca++]i is not required for the expression of the IL 2 receptor, which is expressed even in the presence of extremely low external calcium concentrations. In contrast, IL 2 production requires an increase in [Ca++]i and does not occur in the absence of extracellular free calcium. IL 2 production appears to be the critical step requiring transmembrane calcium flux. In the absence of transmembrane calcium flux and subsequent IL 2 production, lectins are not able to trigger DNA synthesis and cell proliferation.