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

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Title
Distinct requirements for activation-induced cell surface expression of preformed Fas/CD95 ligand and cytolytic granule markers in T cells.
Journal
Cell Death and Differentiation
Author(s)
Kassahn D., Nachbur U., Conus S., Micheau O., Schneider P., Simon H.U., Brunner T.
ISSN
1476-5403
Publication state
Published
Issued date
01/2009
Peer-reviewed
Oui
Volume
16
Number
1
Pages
115-124
Language
english
Abstract
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.
Keywords
Animals, Antigens, CD, Apoptosis, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cell Degranulation, Enzyme Activation, Fas Ligand Protein, Gene Expression Regulation, Humans, Ionophores, Jurkat Cells, Killer Cells, Natural, Lymphocyte Activation, Lysosome-Associated Membrane Glycoproteins, Membrane Glycoproteins, Mice, Phorbol Esters, Protein Kinases, Secretory Vesicles, Transcription, Genetic
Pubmed
Web of science
Open Access
Yes
Create date
13/02/2009 20:10
Last modification date
20/08/2019 15:28
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