Role of Calcium Influx in Cytotoxic T Lymphocyte Lytic Granule Exocytosis during Target Cell Killing

One mechanism cytotoxic T lymphocytes use to kill targets is exocytosis of cytotoxic agents from lytic granules, a process that requires Ca 2+ influx. We investigated the role of Ca 2+ influx in granule exocytosis using TALL-104 human leukemic cytotoxic T cells triggered via a bispecific antibody co...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2001-11, Vol.15 (5), p.847-859
Main Authors: Lyubchenko, Taras A., Wurth, Georjeana A., Zweifach, Adam
Format: Article
Language:English
Subjects:
Calcium - immunology
Calcium - metabolism
Cytotoxicity, Immunologic
Exocytosis - immunology
Humans
Ion Transport - immunology
Secretory Vesicles - immunology
T-Lymphocytes, Cytotoxic - immunology
T-Lymphocytes, Cytotoxic - metabolism
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Summary:One mechanism cytotoxic T lymphocytes use to kill targets is exocytosis of cytotoxic agents from lytic granules, a process that requires Ca 2+ influx. We investigated the role of Ca 2+ influx in granule exocytosis using TALL-104 human leukemic cytotoxic T cells triggered via a bispecific antibody containing an anti-CD3 F(ab′) to kill Raji B lymphoma cells. Using a novel fluorescence method, we detected target-directed release of ∼15% of lytic granules during killing. Consistent with previous work, we observed sustained CTL Ca 2+ gradients during killing, but gradients reflect the behavior of Fura-2 in granules. Rapid imaging experiments suggest that Ca 2+ channels are not polarized during killing, indicating that Ca 2+ influx does not direct granule reorientation. Furthermore, we find that Ca 2+ acts via a high-affinity interaction to promote granule exocytosis.
ISSN:1074-7613
1097-4180
DOI:10.1016/S1074-7613(01)00233-3