The Journal of Experimental Medicine
Avanti Polar Lipids
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 2 September 2003. doi:10.1084/jem.20021358
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Material Index
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 Drappa, J.
Right arrow Articles by King, P. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Drappa, J.
Right arrow Articles by King, P. D.
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?
© Rockefeller University Press, 0022-1007/2003/9/809 $5.00
The Journal of Experimental Medicine, Volume 198, Number 5, 809-821

Impaired T Cell Death and Lupus-like Autoimmunity in T Cell–specific Adapter Protein–deficient Mice

Jorn Drappa1, Lynn A. Kamen1,2, Elena Chan1, Maria Georgiev1, Dalit Ashany1, Francesc Marti1,2 and Philip D. King1,2

1 Research Division, Hospital for Special Surgery, Weill Medical College and Graduate School of Medical Sciences of Cornell University, New York, NY 10021
2 Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109

Address correspondence to Philip D. King, University of Michigan Medical School, Department of Microbiology and Immunology, 6606 Medical Science Building II, Ann Arbor, MI 48109. Phone: (734) 615-9073; Fax: (734) 764-3562; email: kingp{at}umich.edu

T cell–specific adaptor protein (TSAd) is a T lineage–restricted signaling adaptor molecule that is thought to participate in the assembly of intracellular signaling complexes in T cells. Previous studies of TSAd-deficient mice have revealed a role for TSAd in the induction of T cell interleukin 2 secretion and proliferation. We now show that TSAd-deficient mice are susceptible to lupus-like autoimmune disease. On the nonautoimmune-prone C57BL/6 genetic background, TSAd deficiency results in hypergammaglobulinemia that affects all immunoglobulin (Ig)G subclasses. Older C57BL/6 TSAd-deficient mice (1 yr of age) accumulate large numbers of activated T and B cells in spleen, produce autoantibodies against a variety of self-targets including single stranded (ss) and double stranded (ds) DNA, and, in addition, develop glomerulonephritis. We further show that immunization of younger C57BL/6 TSAd-deficient mice (at age 2 mo) with pristane, a recognized nonspecific inflammatory trigger of lupus, results in more severe glomerulonephritis compared with C57BL/6 controls and the production of high titer ss and ds DNA antibodies of the IgG subclass that are not normally produced by C57BL/6 mice in this model. The development of autoimmunity in TSAd-deficient mice is associated with defective T cell death in vivo. These findings illustrate the role of TSAd as a critical regulator of T cell death whose absence promotes systemic autoimmunity.

Key Words: apoptosis • autoimmunity • T lymphocyte • signal transduction • glomerulonephritis


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