Fas ligand (CD95L) protects neurons against perforin-mediated T lymphocyte cytotoxicity

Détails

ID Serval
serval:BIB_A70CC47C441E
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Fas ligand (CD95L) protects neurons against perforin-mediated T lymphocyte cytotoxicity
Périodique
Journal of Immunology
Auteur(s)
Medana  I., Li  Z., Flugel  A., Tschopp  J., Wekerle  H., Neumann  H.
ISSN
0022-1767 (Print)
Statut éditorial
Publié
Date de publication
07/2001
Volume
167
Numéro
2
Pages
674-81
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jul 15
Résumé
Previous work showed that neurons of the CNS are protected against perforin-mediated T cell cytotoxicity, but are susceptible to Fas-mediated apoptosis. In this study, we report that Fas ligand (FasL) expression by neurons is involved in protection against perforin-mediated T cell cytotoxicity. Gene transcripts for FasL were identified in single murine hippocampal neurons by RT-PCR combined with patch clamp electrophysiology, and constitutive expression of FasL protein was confirmed in neurons by immunohistochemistry. Neurons derived from wild-type C57BL/6 (BL6) mice and mutant BL6.gld mice lacking functional FasL were confronted with allogeneic CTLs and continuously monitored in real time for changes in levels of intracellular calcium ([Ca(2+)](i)), an indicator of cytotoxic damage. Perforin-mediated plasma membrane lysis, characterized by rapid, massive [Ca(2+)](i) influx into the target cells within 0.5 h, was not detected in wild-type neurons. In striking contrast, FasL-deficient neurons showed rapid increase in [Ca(2+)](i) within 0.5 h, reflecting perforin-dependent cell lysis. FasL seems to protect neurons by blocking degranulation of CTLs, since CD3-induced release of cytotoxic granules was reduced by coapplication of Fas-specific Abs or rFasL.
Mots-clé
Animals Antigens, CD3/pharmacology Antigens, CD95/*metabolism Apoptosis/genetics/immunology Cells, Cultured Cytoplasmic Granules/immunology/secretion *Cytotoxicity, Immunologic/genetics Fas Ligand Protein Ligands Lymphocyte Activation/genetics/immunology Membrane Glycoproteins/*antagonists & inhibitors/biosynthesis/*physiology/*toxicity Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Mice, Mutant Strains Neurons/cytology/*immunology/metabolism Pore Forming Cytotoxic Proteins T-Lymphocytes, Cytotoxic/*immunology
Pubmed
Web of science
Création de la notice
24/01/2008 16:18
Dernière modification de la notice
20/08/2019 16:11
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