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PMID: 15007096 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

CD152 (CTLA-4) determines the unequal resistance of Th1 and Th2 cells against activation-induced cell death by a mechanism requiring PI3 kinase function.

The Journal of experimental medicine ·Vol. 199 ·No. 6 ·2004-03-15 ·Pages 831-42

Pandiyan P, Gärtner D, Soezeri O, Radbruch A, Schulze-Osthoff K, Brunner-Weinzierl MC

Abstract

Survival of antigen-experienced T cells is essential for the generation of adaptive immune responses. Here, we show that the genetic and antibody-mediated inactivation of CD152 (cytotoxic T lymphocyte antigen 4) in T helper (Th) effector cells reduced the frequency of nonapoptotic cells in a completely Fas/Fas ligand (FasL)-dependent manner. CD152 cross-linking together with stimulation of CD3 and CD28 on activated Th2 cells prevented activation-induced cell death (AICD) as a result of reduced Fas and FasL expression. Apoptosis protection conferred by CD152 correlated with the up-regulation of Bcl-2 and was mediated by phosphatidylinositol 3 kinase, which prevented FasL expression through the inhibitory phosphorylation of Forkhead transcription factor FKHRL1. We show that signals induced by CD152 act directly on activated T lymphocytes and, due to its differential surface expression on activated Th1 and Th2 cells, induce resistance to AICD mainly in Th2 cells.

MeSH Terms
Animals Antigens, CD Antigens, Differentiation/metabolism Apoptosis/immunology,physiology CTLA-4 Antigen Cell Cycle/physiology DNA Primers DNA-Binding Proteins/metabolism Fas Ligand Protein Fluorescent Antibody Technique/methods Forkhead Box Protein O3 Forkhead Transcription Factors Gene Expression Regulation Genes, bcl-2/physiology Genotype Image Cytometry Immunoblotting Membrane Glycoproteins/metabolism Mice Mice, Transgenic Microspheres Phosphatidylinositol 3-Kinases/metabolism Polymerase Chain Reaction Signal Transduction/physiology Th1 Cells/immunology,metabolism,physiology Th2 Cells/immunology,metabolism,physiology Transcription Factors/metabolism
Chemicals
Antigens, CD Antigens, Differentiation CTLA-4 Antigen Ctla4 protein, mouse DNA Primers DNA-Binding Proteins Fas Ligand Protein Fasl protein, mouse Forkhead Box Protein O3 Forkhead Transcription Factors FoxO3 protein, mouse Membrane Glycoproteins Transcription Factors Phosphatidylinositol 3-Kinases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Pandiyan Pushpa
Deutsches Rheuma-Forschungszentrum, Schumannstrasse 21/22, 10117 Berlin, Germany.
Gärtner Dagmar
Soezeri Osman
Radbruch Andreas
Schulze-Osthoff Klaus
Brunner-Weinzierl Monika C
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.20031058
Published
2004-03-15
Epub
2004-00-08
Pages
831-42
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2212725
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.20031058 PMC Full Text View journal details
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