The role of macrophages in T cell-mediated autoimmune diabetes in nonobese diabetic mice
We have shown previously that the inactivation of macrophages in nonobese diabetic (NOD) mice results in the prevention of diabetes; however, the mechanisms involved remain unknown. In this study, we found that T cells in a macrophage-depleted environment lost their ability to differentiate into bet...
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Published in | The Journal of experimental medicine Vol. 189; no. 2; pp. 347 - 358 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
United States
The Rockefeller University Press
18.01.1999
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Subjects | |
Online Access | Get full text |
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Summary: | We have shown previously that the inactivation of macrophages in nonobese diabetic (NOD) mice results in the prevention of diabetes; however, the mechanisms involved remain unknown. In this study, we found that T cells in a macrophage-depleted environment lost their ability to differentiate into beta cell-cytotoxic T cells, resulting in the prevention of autoimmune diabetes, but these T cells regained their beta cell-cytotoxic potential when returned to a macrophage-containing environment. To learn why T cells in a macrophage-depleted environment lose their ability to kill beta cells, we examined the islet antigen-specific immune response and T cell activation in macrophage-depleted NOD mice. There was a shift in the immune balance, a decrease in the T helper cell type 1 (Th1) immune response, and an increase in the Th2 immune response, due to the reduced expression of the macrophage-derived cytokine IL-12. As well, there was a deficit in T cell activation, evidenced by significant decreases in the expression of Fas ligand and perforin. The administration of IL-12 substantially reversed the prevention of diabetes in NOD mice conferred by macrophage depletion. We conclude that macrophages play an essential role in the development and activation of beta cell-cytotoxic T cells that cause beta cell destruction, resulting in autoimmune diabetes in NOD mice. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 Address correspondence to Ji-Won Yoon, Laboratory of Viral Immunopathogenesis of Diabetes, Julia McFarlane Diabetes Research Centre, Faculty of Medicine, The University of Calgary, 3330 Hospital Dr. Northwest, Calgary, Alberta, Canada T2N 4N1. Phone: 403-220-4569; Fax: 403-270-7526; E-mail: yoon@acs.ucalgary.ca |
ISSN: | 0022-1007 1540-9538 |
DOI: | 10.1084/jem.189.2.347 |