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  • Title: Uptake of extracellular Ca2+ and not recruitment from internal stores is essential for T lymphocyte proliferation.
    Author: Gelfand EW, Cheung RK, Mills GB, Grinstein S.
    Journal: Eur J Immunol; 1988 Jun; 18(6):917-22. PubMed ID: 3133231.
    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+]i 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 (IL 2) secretion and cell proliferation. To determine the relative effects of the initial and sustained phases of [Ca2+]i change, IL 2 secretion and cell proliferation, we introduced into the cell 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), 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 IL 2 receptor expression, IL 2 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.
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