Comparison of Fas(Apo-1/CD95)- and perforin-mediated cytotoxicity in primary T lymphocytes

Details

Ressource 1Download: serval:BIB_F6B75BB52B19.P001 (5032.56 [Ko])
State: Public
Version: author
License: Not specified
It was possible to publish this article open access thanks to a Swiss National Licence with the publisher.
Serval ID
serval:BIB_F6B75BB52B19
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Comparison of Fas(Apo-1/CD95)- and perforin-mediated cytotoxicity in primary T lymphocytes
Journal
International Immunology
Author(s)
Lowin  B., Mattman  C., Hahne  M., Tschopp  J.
ISSN
0953-8178 (Print)
Publication state
Published
Issued date
01/1996
Volume
8
Number
1
Pages
57-63
Notes
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jan
Abstract
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.
Keywords
Animals Antigens, CD95/biosynthesis/*immunology Apoptosis Blotting, Western Calcium/metabolism Cell Line Cells, Cultured *Cytotoxicity, Immunologic Flow Cytometry Membrane Glycoproteins/*immunology Mice Mice, Inbred C57BL Mice, Inbred DBA Pore Forming Cytotoxic Proteins Protein Biosynthesis RNA/biosynthesis T-Lymphocytes, Cytotoxic/*immunology
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 16:18
Last modification date
25/09/2019 7:11
Usage data