The Journal of Experimental Medicine
MBL International Tel: 800.200.5459 CLICK HERE
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 8 March 2004 doi:10.1084/jem.20031058
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 6, 831-842
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Pandiyan, P.
Right arrow Articles by Brunner-Weinzierl, M. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pandiyan, P.
Right arrow Articles by Brunner-Weinzierl, M. C.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
CD152 (CTLA-4) Determines the Unequal Resistance of Th1 and Th2 Cells against Activation-induced Cell Death by a Mechanism Requiring PI3 Kinase Function

Pushpa Pandiyan1, Dagmar Gärtner1, Osman Soezeri1, Andreas Radbruch1, Klaus Schulze-Osthoff2, and Monika C. Brunner-Weinzierl1,3

1 Deutsches Rheuma-Forschungszentrum Berlin, 2 Institut für Molekulare Medizin, Universität Düsseldorf, and 3 Medizinische Kliniken der Humboldt-Universität zu Berlin, Charité, 10117 Berlin, Germany

Address correspondence to Monika C. Brunner-Weinzierl, Deutsches Rheuma-Forschungszentrum, Schumannstrasse 21/22, 10117 Berlin, Germany. Phone: 49-30-28460-721; Fax: 49-30-28460-603; email: brunner{at}drfz.de

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.

Key Words: costimulation • apoptosis • survival • signal transduction • FasL

Abbreviations used in this paper: AICD, activation-induced cell death; CFSE, 5,6-carboxyfluorescein diacetate succinimidyl ester; dB-cAMP, dibutyryl cAMP; FasL, Fas ligand; tg, transgenic; PI, propidium iodide; PI3 K, phosphatidylinositol 3 kinase; TUNEL, TdT-mediated dUTP nick-end labeling.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS