Role of calcium influx in cytotoxic T lymphocyte lytic granule exocytosis during target cell killing

Immunity. 2001 Nov;15(5):847-59. doi: 10.1016/s1074-7613(01)00233-3.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Calcium / immunology*
  • Calcium / metabolism
  • Cytotoxicity, Immunologic*
  • Exocytosis / immunology
  • Humans
  • Ion Transport / immunology
  • Secretory Vesicles / immunology
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism

Substances

  • Calcium