The Journal of Experimental Medicine
Avanti Polar Lipids, Inc.
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 10 October 2005 doi:10.1084/jem.20050003
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 202, Number 8, 1099-1108
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 226K)
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 Davey, G. M.
Right arrow Articles by Heath, W. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Davey, G. M.
Right arrow Articles by Heath, W. R.
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?

ARTICLE

 SOCS-1 regulates IL-15–driven homeostatic proliferation of antigen-naive CD8 T cells, limiting their autoimmune potential

Gayle M. Davey1, Robyn Starr1, Ann L. Cornish1, J. Theodore Burghardt2, Warren S. Alexander1, Francis R. Carbone3, Charles D. Surh2, and William R. Heath1

1 The Walter and Eliza Hall Institute of Medical Research, Parkville, 3050 Victoria, Australia
2 Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037
3 Department of Microbiology and Immunology, University of Melbourne, Parkville, 3052 Victoria, Australia

CORRESPONDENCE William R. Heath: heath{at}wehi.edu.au

Mice that are deficient in suppressor of cytokine signaling–1 (SOCS-1) succumb to neonatal mortality that is associated with extensive cellular infiltration of many tissues. T cells seem to be necessary for disease, which can be alleviated largely by neutralizing interferon-{gamma}. Examining T cell receptor (TCR) specificity shows that even monospecific T cells can mediate disease in SOCS-1–deficient mice, although disease onset is substantially faster with a polyclonal T cell repertoire. A major phenotype of SOCS-1–/– mice is the accumulation of CD44highCD8+ peripheral T cells. We show that SOCS-1–deficient CD8, but not CD4, T cells proliferate when transferred into normal (T cell–sufficient) mice, and that this is dependent on two signals: interleukin (IL)-15 and self-ligands that are usually only capable of stimulating homeostatic expansion in T cell–deficient mice. Our findings reveal that SOCS-1 normally down-regulates the capacity of IL-15 to drive activation and proliferation of naive CD8 T cells receiving TCR survival signals from self-ligands. We show that such dysregulated proliferation impairs the deletion of a highly autoreactive subset of CD8 T cells, and increases their potential for autoimmunity. Therefore, impaired deletion of highly autoreactive CD8 T cells, together with uncontrolled activation of naive CD8 T cells by homeostatic survival ligands, may provide a basis for the T cell–mediated disease of SOCS-1–/– mice.

Abbreviations used: CFSE, carboxy fluorescein diacetate succinimidyl ester; poly I:C, polyinosine-polycytidylic acid; SOCS-1, suppressor of cytokine signaling–1

R. Starr's present address is St. Vincent's Institute, Fitzroy, 3065 Victoria, Australia.

A.L. Cornish's present address is Department of Microbiology and Immunology, University of Melbourne, Parkville, 3052 Victoria, Australia.


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