Regulation of Fas(Apo-1/CD95)- and perforin-mediated lytic pathways of primary cytotoxic T lymphocytes by the protooncogene bcl-2

Details

Serval ID
serval:BIB_2AA39A25A4EC
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Regulation of Fas(Apo-1/CD95)- and perforin-mediated lytic pathways of primary cytotoxic T lymphocytes by the protooncogene bcl-2
Journal
European Journal of Immunology
Author(s)
Schroter  M., Lowin  B., Borner  C., Tschopp  J.
ISSN
0014-2980 (Print)
Publication state
Published
Issued date
12/1995
Volume
25
Number
12
Pages
3509-13
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Dec
Abstract
Cytotoxic T cells (CTL) induce cell death of their target cells either by the surface interaction between Fas ligand and Fas or by the release of perforin and granzymes. Both lytic pathways induce apoptosis yet it is not known whether identical or distinct apoptotic pathways are activated. The protooncogene bcl-2 is known to protect various hematopoietic cells from apoptosis induced by diverse agents. Here we show that overexpression of the Bcl-2 protein in the murine mastocytoma line P815 or in concanavalin A-activated splenocytes suppresses apoptotic cell death induced by allospecific primary cytotoxic T lymphocytes (CTL) in which only the Fas lytic pathway was functional. Bcl-2 also reduced target cell killing induced by CTL whose lytic activity was dependent on the perforin/granzyme pathway only. These data provide evidence that, in the target cells studied here, both perforin/granzyme and Fas apoptotic pathways are modulated by Bcl-2 and suggest that these two pathways converge at a step prior to Bcl-2 inhibition.
Keywords
Animals Antigens, CD95/drug effects/pharmacology Base Sequence Cytotoxicity, Immunologic Mast-Cell Sarcoma/genetics Membrane Glycoproteins/drug effects/pharmacology Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Transgenic Molecular Sequence Data Pore Forming Cytotoxic Proteins Proto-Oncogene Proteins/*genetics/pharmacology Proto-Oncogene Proteins c-bcl-2 Proto-Oncogenes/*immunology/*physiology T-Lymphocytes, Cytotoxic/drug effects/*immunology Tumor Cells, Cultured
Pubmed
Web of science
Create date
24/01/2008 15:18
Last modification date
20/08/2019 13:10
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