IL-4 potentiates activated T cell apoptosis via an IL-2-dependent mechanism

Details

Serval ID
serval:BIB_43345B83AA81
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
IL-4 potentiates activated T cell apoptosis via an IL-2-dependent mechanism
Journal
Journal of Immunology
Author(s)
Zhang  J., Bardos  T., Shao  Q., Tschopp  J., Mikecz  K., Glant  T. T., Finnegan  A.
ISSN
0022-1767 (Print)
Publication state
Published
Issued date
04/2003
Volume
170
Number
7
Pages
3495-503
Notes
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Apr 1
Abstract
Activation-induced cell death (AICD) of T cells is one of the major mechanisms of peripheral tolerance. The regulation of AICD by IL-4 is poorly understood. In this study, we report that AICD in IL-4-deficient T cells is significantly reduced compared with that in wild-type T cells. This impaired AICD correlates with the failure to induce degradation of cellular FLIP. IL-4-mediated enhancement of AICD and cellular FLIP degradation requires a Janus kinase/STAT-6 signaling pathway. Unexpectedly, these effects of IL-4 could be blocked by a neutralizing anti-IL-2 Ab, and addition of rIL-2 could completely restore the defective AICD in IL-4-deficient T cells. Furthermore, IL-4 regulates the T cell thresholds for IL-2 signaling during AICD. These data suggest that IL-4 promotes AICD via an IL-2-dependent mechanism.
Keywords
Adjuvants, Immunologic/deficiency/genetics/*physiology Animals Antigens, CD95/metabolism Apoptosis/genetics/*immunology CASP8 and FADD-Like Apoptosis Regulating Protein Carrier Proteins/metabolism Cells, Cultured Drug Synergism Fas Ligand Protein Interleukin-2/*physiology Interleukin-4/deficiency/genetics/*physiology *Intracellular Signaling Peptides and Proteins Ligands *Lymphocyte Activation/genetics Membrane Glycoproteins/biosynthesis Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Proto-Oncogene Proteins c-bcl-2/biosynthesis Receptors, Antigen, T-Cell/physiology STAT6 Transcription Factor Signal Transduction/immunology T-Lymphocyte Subsets/*cytology/*immunology/metabolism Trans-Activators/deficiency/genetics/physiology Up-Regulation/immunology
Pubmed
Web of science
Create date
24/01/2008 15:18
Last modification date
20/08/2019 13:46
Usage data