Distinct requirements for activation-induced cell surface expression of preformed Fas/CD95 ligand and cytolytic granule markers in T cells

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2009
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Kassahn, Daniela
Nachbur, Ueli
Conus, Sébastien
Micheau, Olivier
Simon, Hans-Uwe
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Cell Death and Differentiation. 2009, 16(1), pp. 115-124. ISSN 1350-9047. eISSN 1476-5403. Available under: doi: 10.1038/cdd.2008.133
Zusammenfassung

Fas (CD95/Apo-1) ligand is a potent inducer of apoptosis and one of the major killing effector mechanisms of cytotoxic T cells. Thus, Fas ligand activity has to be tightly regulated, involving various transcriptional and post-transcriptional processes. For example, preformed Fas ligand is stored in secretory lysosomes of activated T cells, and rapidly released by degranulation upon reactivation. In this study, we analyzed the minimal requirements for activation-induced degranulation of Fas ligand. T cell receptor activation can be mimicked by calcium ionophore and phorbol ester. Unexpectedly, we found that stimulation with phorbol ester alone is sufficient to trigger Fas ligand release, whereas calcium ionophore is neither sufficient nor necessary. The relevance of this process was confirmed in primary CD4+ and CD8+ T cells and NK cells. Although the activation of protein kinase(s) was absolutely required for Fas ligand degranulation, protein kinase C or A were not involved. Previous reports have shown that preformed Fas ligand co-localizes with other markers of cytolytic granules. We found, however, that the activation-induced degranulation of Fas ligand has distinct requirements and involves different mechanisms than those of the granule markers CD63 and CD107a/Lamp-1. We conclude that activation-induced degranulation of Fas ligand in cytotoxic lymphocytes is differently regulated than other classical cytotoxic granule proteins.

Zusammenfassung in einer weiteren Sprache
Fachgebiet (DDC)
570 Biowissenschaften, Biologie
Schlagwörter
cytotoxic T cells, Fas ligand, cytotoxic granules, degranulation, protein kinases
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ISO 690KASSAHN, Daniela, Ueli NACHBUR, Sébastien CONUS, Olivier MICHEAU, Pascal SCHNEIDER, Hans-Uwe SIMON, Thomas BRUNNER, 2009. Distinct requirements for activation-induced cell surface expression of preformed Fas/CD95 ligand and cytolytic granule markers in T cells. In: Cell Death and Differentiation. 2009, 16(1), pp. 115-124. ISSN 1350-9047. eISSN 1476-5403. Available under: doi: 10.1038/cdd.2008.133
BibTex
@article{Kassahn2009-01Disti-14260,
  year={2009},
  doi={10.1038/cdd.2008.133},
  title={Distinct requirements for activation-induced cell surface expression of preformed Fas/CD95 ligand and cytolytic granule markers in T cells},
  number={1},
  volume={16},
  issn={1350-9047},
  journal={Cell Death and Differentiation},
  pages={115--124},
  author={Kassahn, Daniela and Nachbur, Ueli and Conus, Sébastien and Micheau, Olivier and Schneider, Pascal and Simon, Hans-Uwe and Brunner, Thomas}
}
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