Skip Navigation



International Immunology Advance Access published online on October 5, 2004
International Immunology, doi:10.1093/intimm/dxh167
© 2004 by The Japanese Society for Immunology
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
16/11/1657    most recent
dxh167v1
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 Qin, H.
Right arrow Articles by Tan, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Qin, H.
Right arrow Articles by Tan, R.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Received March 10, 2003
Accepted August 30, 2004

Article

Progression of spontaneous autoimmune diabetes is associated with a switch in the killing mechanism used by autoreactive CTL

Huilian Qin 1, Jacqueline D. Trudeau 1, Gregor S. D. Reid 2, I-Fang Lee 1, Jan P. Dutz 3, Pere Santamaria 4, C. Bruce Verchere 1, and Rusung Tan 1*

1 Department of Pathology and Laboratory Medicine, University of British Columbia, BC's Children's Hospital, 4480 Oak Street, Vancouver, British Columbia, V6H 3V4, Canada
2 Department of Pediatrics, University of British Columbia, BC's Children's Hospital, 4480 Oak Street, Vancouver, British Columbia, V6H 3V4, Canada
3 Department of Medicine, University of British Columbia, BC's Children's Hospital, 4480 Oak Street, Vancouver, British Columbia, V6H 3V4, Canada
4 Department of Microbiology and Infectious Diseases and Julia McFarlane Diabetes Research Centre, Faculty of Medicine, University of Calgary, Health Sciences Centre, 3330 Hospital Drive NW, Calgary, Alberta, T2N 4N1, Canada

* To whom correspondence should be addressed. E-mail: roo{at}interchange.ubc.ca.


  Abstract

Autoimmune (type 1) diabetes mellitus results from the destruction of insulin-producing pancreatic {beta}-cells by T lymphocytes. {beta}-cell death that is induced by autoreactive CTL in diabetes involves both Fas/Fas ligand (FasL)- and perforin/granzyme-mediated pathways, although their relative contributions during the progression of the disease remain unknown. We demonstrate here that despite the preferential use of the Fas/FasL pathway for cytolysis of {beta}-cell targets, transgenic {beta}-cell-specific CTL were able to kill targets via the perforin pathway when triggered by a higher affinity stimulus. In addition, we show that the killing mechanism used by islet-associated CD8+ T cells from non-obese diabetic mice changed as the mice aged and correspondingly, with the stage of diabetes. These results provide direct evidence for age-related changes in the cytotoxic pathways used by diabetogenic T cells during the progression of autoimmune diabetes.

Keywords: avidity maturation; CTL; Fas; non-obese diabetic; perforin.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 DiabetesHome page
N. L. Dudek, H. E. Thomas, L. Mariana, R. M. Sutherland, J. Allison, E. Estella, E. Angstetra, J. A. Trapani, P. Santamaria, A. M. Lew, et al.
Cytotoxic T-Cells From T-Cell Receptor Transgenic NOD8.3 Mice Destroy {beta}-Cells via the Perforin and Fas Pathways
Diabetes, September 1, 2006; 55(9): 2412 - 2418.
[Abstract] [Full Text] [PDF]


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.