Uptake of extracellular Ca2+ and not recruitment from internal stores is essential for T lymphocyte proliferation.
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.
D000911:Antibodies, Monoclonal / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D002021:Buffers; D002118:Calcium / Q000378:metabolism*; D004533:Egtazic Acid / Q000031:analogs & derivatives; D005110:Extracellular Space / Q000378:metabolism*; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation; D010835:Phytohemagglutinins; D011971:Receptors, Immunologic / Q000378:metabolism; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D002021:Buffers; D007376:Interleukin-2; D010835:Phytohemagglutinins; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium; D013936:Thymidine