Regulation of Fas ligand-induced apoptosis by TNF

Details

Serval ID
serval:BIB_D9A634D5ADD4
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Regulation of Fas ligand-induced apoptosis by TNF
Journal
Journal of Immunology
Author(s)
Elzey  B. D., Griffith  T. S., Herndon  J. M., Barreiro  R., Tschopp  J., Ferguson  T. A.
ISSN
0022-1767 (Print)
Publication state
Published
Issued date
09/2001
Volume
167
Number
6
Pages
3049-56
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Sep 15
Abstract
Fas ligand (FasL, CD95L) expression helps control inflammatory reactions in immune privileged sites such as the eye. Cellular activation is normally required to render lymphoid cells sensitive to FasL-induced death; however, both activated and freshly isolated Fas(+) lymphoid cells are efficiently killed in the eye. Thus, we examined factors that might regulate cell death in the eye. TNF levels rapidly increased in the eye after the injection of lymphoid cells, and these cells underwent apoptosis within 24 h. Coinjection of anti-TNF Ab with the lymphoid cells blocked this cell death. Furthermore, TNFR2(-/-) T cells did not undergo apoptosis in the eyes of normal mice, while normal and TNFR1(-/-) T cells were killed by apoptosis. In vitro, TNF enhanced the Fas-mediated apoptosis of unactivated T cells through decreased intracellular levels of FLIP and increased production of the pro-apoptotic molecule Bax. This effect was mediated through the TNFR2 receptor. In vivo, intracameral injection of normal or TNFR1(-/-) 2,4,6-trinitrophenyl-coupled T cells into normal mice induced immune deviation, but TNFR2(-/-) 2,4,6-trinitrophenyl-coupled T cells were ineffective. Collectively, our results provide evidence of a role for the p75 TNFR in cell death in that TNF signaling through TNFR2 sensitizes lymphoid cells for Fas-mediated apoptosis. We conclude that there is complicity between apoptosis and elements of the inflammatory response in controlling lymphocyte function in immune privileged sites.
Keywords
Animals Anterior Chamber/*immunology Antigens, CD/genetics/physiology Antigens, CD95/*physiology Apoptosis/drug effects/*physiology Blood-Retinal Barrier CASP8 and FADD-Like Apoptosis Regulating Protein Carrier Proteins/biosynthesis/genetics/physiology Eye Proteins/pharmacology/*physiology Fas Ligand Protein Graft Rejection/*immunology Haptens *Intracellular Signaling Peptides and Proteins Lymphocytes/cytology Membrane Glycoproteins/*physiology Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Picryl Chloride Proto-Oncogene Proteins/biosynthesis/genetics *Proto-Oncogene Proteins c-bcl-2 Receptors, Tumor Necrosis Factor/deficiency/genetics/physiology Receptors, Tumor Necrosis Factor, Type I Receptors, Tumor Necrosis Factor, Type II T-Lymphocyte Subsets/*cytology/transplantation Th2 Cells/immunology Tumor Necrosis Factor-alpha/pharmacology/*physiology bcl-2-Associated X Protein
Pubmed
Web of science
Create date
24/01/2008 15:19
Last modification date
20/08/2019 15:58
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