Uptake of extracellular Ca2+ and not recruitment from internal stores is essential for T lymphocyte proliferation

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Abstract
Changes in free cytosolic calcium concentrations ([Ca2+]i]are thought to be important initiating events in the activation of T lymphocytes. Mitogen‐induced increases in [Ca2+Ii may result from net influx across the plasma membrane and/or release of Ca2+ from intracellular stores. In human T lymphocytes loaded with the fluorescent indicator indo‐1, addition of phytohemagglutinin (PHA) or the anti‐CD3 antibody UCHT‐1 elicits a biphasic [Ca2+]i response. A major component of the initial transient peak was due to release from internal stores whereas the lower plateau phase was sustained by Ca2+ influx. Previous work suggested that Ca2+ influx is essential for interleukin 2 (IL2) secretion and cell proliferation. To determine the relative effects of the initial and sustained phases of [Ca2+]i change, IL2 secretion and cell proliferation, we introduced into the cell 1, 2‐bis(o‐aminophenoxy)ethane‐N,N,N′,N′‐tet‐raacetic acid (BAFTA), a high affinity intracellular Ca2+ chelator which neither contributes to nor interferes with the fluorescence determinations of [Ca2+]i In cells preloaded with BAPTA, both PHA and UCHT‐1 antibody failed to elicit the transient [Ca2+]i overshoot. Only the plateau phase could be observed in the presence of extracellular Ca2+. In contrast, BAPTA‐loaded cells were found to be fully functional when assessed for IL2 receptor expression, IL2 secretion and cell proliferation. Thus, the mitogen‐induced, maximal but transient increase in [Ca2+]i, contributed to mainly by release of Ca2+ from internal stores, does not appear to be essential for these T cell responses.