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
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
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 16:19
Last modification date
20/08/2019 16:58