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 approximately 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.
Role of calcium influx in cytotoxic T lymphocyte lytic granule exocytosis during target cell killing.
Taras Lyubchenko,Georjeana A. Wurth,Adam Zweifach
Published 2001 in Immunity
ABSTRACT
PUBLICATION RECORD
- Publication year
2001
- Venue
Immunity
- Publication date
2001-11-01
- Fields of study
Biology, Medicine
- Identifiers
- External record
- Source metadata
Semantic Scholar, PubMed
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