Skip Navigation



International Immunology Advance Access published online on April 13, 2004
International Immunology, doi:10.1093/intimm/dxh078
© 2004 by The Japanese Society for Immunology
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
16/5/759    most recent
dxh078v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Xiao, S.
Right arrow Articles by Ju, S.-T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Xiao, S.
Right arrow Articles by Ju, S.-T.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Received November 6, 2003
Accepted February 23, 2004

Article

Changes in sensitivity of peripheral lymphocytes of autoimmune gld mice to FasL-mediated apoptosis reveal a mechanism for the preferential deletion of CD4-CD8-B220+ T cells

Sheng Xiao 1, Xingmin Zhang 2, Koren K. Mann 3, Satoshi Jodo 4, Li Li 5, Wael N. Jarjour 5, Ann Marshak-Rothstein 6, David H. Sherr 7, Shyr-Te Ju 1*

1 Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA 02118, USA; Department of Medicine, Division of Rheumatology and Immunology, University of Virginia, Charlottesville, VA 22908, USA
2 Center for Neurologic Diseases, Harvard Medical School, Boston, MA 02115, USA
3 Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA 02118, USA; Department of Environmental Health, School of Public Health, Boston University School of Medicine, Boston, MA 02118, USA
4 Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA
5 Department of Medicine, Division of Rheumatology and Immunology, University of Virginia, Charlottesville, VA 22908, USA
6 Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA
7 Department of Environmental Health, School of Public Health, Boston University School of Medicine, Boston, MA 02118, USA

* To whom correspondence should be addressed. E-mail: sj8r{at}virginia.edu.


  Abstract

During thymic selection ‘mis-selected’ CD8+ T cells exit to the periphery where they are deleted by a Fas/FasL-mediated mechanism, presumably as a result of activation by self-antigens. In the absence of functional FasL, as is the case in autoimmune gld mice, these ‘mis-selected’ T cells develop into unique Thy1+CD4-CD8- TCR{alpha}{beta}+B220+ lymphocytes [abnormal double negative T (DN T) cells]. Using bioactive FasL-bearing vesicles [FasL vesicle preparation (FasL VP)], we were able to induce acute apoptosis in freshly isolated lymphocytes and to demonstrate that peripheral lymphocytes of gld mice become more sensitive to the FasL-mediated apoptosis as they age. Furthermore, flow cytometric analyses indicated that within this peripheral lymphocyte population, the abnormal DN T cells were preferentially eliminated. The exquisite sensitivity of these abnormal DN T cells is attributed to their increased membrane Fas expression with a concomitant reduction of cytosolic FLIPL. Our data support the hypothesis that specific components of the Fas-mediated apoptotic pathway are modulated in favor of the elimination of auto-reactive T cells as well as those CD8+ T cells that are ‘mis-selected’ in the thymus and escape to the periphery.

Keywords: Keywords: apoptosis, DN T cells, Fas, FLIP, IL-2, T cell deletion


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.