HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by van Halteren, A. G.S. Articles by Wauben, M. H. M. Search for Related Content PubMed PubMed Citation Articles by van Halteren, A. G.S. Articles by Wauben, M. H. M.

T Cell Reactivity to Heat Shock Protein 60 in Diabetes-Susceptible and Genetically Protected Nonobese Diabetic Mice Is Associated with a Protective Cytokine Profile¹

Astrid G.S. van Halteren^2,*,, Bart Mosselman, Bart O. Roep, Willem van Eden, Anne Cooke, Georg Kraal^* and Marca H. M. Wauben

^* Department of Cell Biology and Immunology, Medical Faculty, Vrije Universiteit Amsterdam, Amsterdam, Institute of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, and Department of Immunohematology and Bloodtransfusion, Leiden University Medical Center, Leiden, The Netherlands; and Department of Pathology, Immunology Division, University of Cambridge, Cambridge, United Kingdom

Spontaneous onset of pancreatic cell destruction in the nonobese diabetic (NOD) mouse is preceded by the induction of autoreactive T cells, which recognize a variety of autoantigens. The 60-kDa endogenous (murine) heat shock protein 60 (hsp60) has been proposed to be one of the key autoantigens. Here we demonstrate that subcutaneous immunization of normoglycemic NOD mice with highly homologous mycobacterial or murine hsp60 activates T cells in the spleen that produce high levels of IL-10 upon restimulation in vitro with either hsp60 protein. In time, increasing levels of hsp60-induced IL-10 could be detected in NOD mice, but not in age- and MHC class II-matched BiozziABH mice, which lack any sign of pancreatic inflammation. These results suggest that the IL-10 responses in NOD mice are primarily driven by endogenous inflammation. Genetically protected NOD-asp mice, showing a less progressive development of insulitis, demonstrated a similar increase in hsp60-induced IL-10 in time compared with wild-type NOD mice. Taken together, our results suggest that endogenous hsp60 is not a primary autoantigen in diabetes but is possibly associated with regulation of insulitis. Moreover, the capacity to respond to (self) hsp60 is independent of the MHC class II-associated genetic predisposition to diabetes.

This article has been cited by other articles:

				W van Eden, R van der Zee, P van Kooten, S E Berlo, P M Cobelens, A Kavelaars, C J Heijnen, B Prakken, S Roord, and S Albani Balancing the immune system: Th1 and Th2 Ann Rheum Dis, November 1, 2002; 61(90002): ii25 - 28. [Full Text] [PDF]