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Calcium influx and signaling in cytotoxic T‐lymphocyte lytic granule exocytosis
Author(s) -
PoresFernando Arun T.,
Zweifach Adam
Publication year - 2009
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/j.1600-065x.2009.00809.x
Subject(s) - lytic cycle , exocytosis , cytotoxic t cell , immunological synapse , granule (geology) , calcium , immunology , biology , lymphocyte , t lymphocyte , microbiology and biotechnology , calcium signaling , cytotoxicity , lymphocyte subsets , immune system , signal transduction , medicine , t cell , genetics , endocrinology , secretion , in vitro , t cell receptor , virus , paleontology
Summary: Cytotoxic T lymphocytes (CTLs) kill targets by releasing cytotoxic agents from lytic granules. Killing is a multi‐step process. The CTL adheres to a target, allowing its T‐cell receptors to recognize antigen. This triggers a signal transduction cascade that leads to the polarization of the microtubule cytoskeleton and granules towards the target, followed by exocytosis that occurs specifically at the site of contact. As with cytokine production by helper T cells (Th cells), target cell killing is absolutely dependent on Ca 2+ influx, which is involved in regulating both reorientation and release. Current evidence suggests that Ca 2+ influx in CTLs, as in Th cells, occurs via depletion‐activated channels. The molecules that couple increases in Ca 2+ to reorientation are unknown. The Ca 2+ /calmodulin‐dependent phosphatase calcineurin, which plays a critical role in cytokine production by Th cells, is also involved in lytic granule exocytosis, although the relevant substrates remain to be identified and calcineurin activation is only one Ca 2+ ‐dependent step involved. There are thus striking similarities and important differences between Ca 2+ signals in Th cells and CTLs, illustrating how cells can use similar signal transduction pathways to generate different functional outcomes.