The Journal of Experimental Medicine
Avanti Polar Lipids
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 6 June 1999.
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
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 Garza, K. M.
Right arrow Articles by Ohashi, P. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Garza, K. M.
Right arrow Articles by Ohashi, P. S.
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?
© The Rockefeller University Press, 0022-1007/2000/6/2021/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 11, June 5, 2000 2021-2028

BDR

Role of Antigen-presenting Cells in Mediating Tolerance and Autoimmunity

Kristine M. Garzaa, Steven M. Chana, Rakesh Suria, Linh T. Nguyena, Bernhard Odermattb, Stephen P. Schoenbergerc, and Pamela S. Ohashia
a Departments of Medical Biophysics and Immunology, Ontario Cancer Institute, Toronto, Ontario M5G 2M9, Canada
b Institute of Pathology, Department of Experimental Pathology, University Hospital, 8091 Zurich, Switzerland
c Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, San Diego, California 92121

Correspondence to: Pamela S. Ohashi, Ontario Cancer Institute, 610 University Ave., Toronto, ON M5G 2M9, Canada. Tel:416-946-2000 Fax:416-946-2086 E-mail:pohashi{at}oci.utoronto.ca.

The mechanisms that determine whether receptor stimulation leads to lymphocyte tolerance versus activation remain poorly understood. We have used rat insulin promoter (RIP)-gp/P14 double-transgenic mice expressing the lymphocytic choriomeningitis virus (LCMV) glycoprotein (gp) on pancreatic ß-islet cells together with T cells expressing an LCMV-gp–specific T cell receptor to assess the requirements for the induction of autoimmunity. Our studies have shown that administration of the gp peptide gp33 leads to the activation of P14-transgenic T cells, as measured by the upregulation of activation markers and the induction of effector cytotoxic activity. This treatment also leads to expansion and deletion of P14 T cells. Despite the induction of cytotoxic T lymphocyte activity, peptide administration is not sufficient to induce diabetes. However, the administration of gp peptide together with an activating anti-CD40 antibody rapidly induces diabetes. These findings suggest that the induction of tolerance versus autoimmunity is determined by resting versus activated antigen-presenting cells.

Key Words: activation, CTL, diabetes, CD40, costimulation


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