Titre
Comparison of Fas(Apo-1/CD95)- and perforin-mediated cytotoxicity in primary T lymphocytes
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Lowin, B.
Auteure/Auteur
Mattman, C.
Auteure/Auteur
Hahne, M.
Auteure/Auteur
Tschopp, J.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
0953-8178
Statut éditorial
Publié
Date de publication
1996-01
Volume
8
Numéro
1
Première page
57
Dernière page/numéro d’article
63
Notes
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jan
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jan
Résumé
Cytolytic T lymphocytes kill target cells by two independent cytolytic mechanisms. One pathway depends on the polarized secretion of granule-stored proteins including perforin and granzymes, causing target cell death through membrane and DNA damage. The second cytolytic effector system relies on the interaction of the Fas ligand (Fasl) on the effector cell with its receptor (Fas) on the target cell, leading to apoptotic cell death. Using mixed lymphocyte culture (MLC)-derived primary T lymphocytes of perforin-knockout and gld (with non-functional FasL) mice, the molecular basis of the two killing mechanisms was compared. The activity of both pathways was dependent on extracellular Ca2+. Incubation of MLC-stimulated primary T cells with protein synthesis inhibitors prior to TCR triggering impaired FasL cell surface expression and abolished cytolytic activity, although the cells exhibited an intracellular pool of FasL. The perforin-dependent mechanism induced cell death more rapidly, although both pathways ultimately showed similar killing efficiencies. Both pathways induced comparable levels of DNA degradation, but Fas-induced membrane damage was less pronounced. We conclude that upon TCR triggering FasL may be recruited in part from pre-existing intracellular stores. However, efficient induction of target cell death still depends on the continuous biosynthesis of FasL molecules.
Sujets
PID Serval
serval:BIB_F6B75BB52B19
PMID
Open Access
Oui
Date de création
2008-01-24T14:18:15.556Z
Date de création dans IRIS
2025-05-21T06:53:20Z
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Nom
REF.pdf
Version du manuscrit
published
Taille
4.91 MB
Format
Adobe PDF
PID Serval
serval:BIB_F6B75BB52B19.P001
URN
urn:nbn:ch:serval-BIB_F6B75BB52B196
Somme de contrôle
(MD5):5faa23788e8a1d12a29919f0faeb8ea0