Expression of diabetes-associated genes by dendritic cells and CD4 T cells drives the loss of tolerance in nonobese diabetic mice

Hamilton-Williams, Emma E., Martinez, Xavier, Clark, Jan, Howlett, Sarah, Hunter, Kara M., Rainbow, Daniel B., Wen, Li, Shlomchik, Mark J., Katz, Jonathan D., Beilhack, Georg F., Wicker, Linda S. and Sherman, Linda A. (2009) Expression of diabetes-associated genes by dendritic cells and CD4 T cells drives the loss of tolerance in nonobese diabetic mice. Journal of Immunology, 183 3: 1533-1541. doi:10.4049/jimmunol.0900428


Author Hamilton-Williams, Emma E.
Martinez, Xavier
Clark, Jan
Howlett, Sarah
Hunter, Kara M.
Rainbow, Daniel B.
Wen, Li
Shlomchik, Mark J.
Katz, Jonathan D.
Beilhack, Georg F.
Wicker, Linda S.
Sherman, Linda A.
Title Expression of diabetes-associated genes by dendritic cells and CD4 T cells drives the loss of tolerance in nonobese diabetic mice
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 0022-1767
1550-6606
Publication date 2009-08
Sub-type Article (original research)
DOI 10.4049/jimmunol.0900428
Volume 183
Issue 3
Start page 1533
End page 1541
Total pages 9
Place of publication Bethesda, MD, United States
Publisher American Association of Immunologists
Language eng
Abstract In humans and NOD mice, defects in immune tolerance result in the spontaneous development of type-1-diabetes. Recent studies have ascribed a breakdown in tolerance to dysfunction in regulatory T cells that is secondary to reduced IL-2 production by T cells having the NOD diabetes susceptibility region insulin-dependent diabetes 3 (Idd3). In this study, we demonstrate a peripheral tolerance defect in the dendritic cells of NOD mice that is independent of regulatory T cells. NOD CD8 T cells specific for islet Ags fail to undergo deletion in the pancreatic lymph nodes. Deletion was promoted by expression of the protective alleles of both Idd3 (Il2) and Idd5 in dendritic cells. We further identify a second tolerance defect that involves endogenous CD4 T cell expression of the disease-promoting NOD alleles of these genetic regions. Pervasive insulitis can be reduced by expression of the Idd3 and Idd5 protective alleles by either the Ag-presenting cell or lymphocytes.
Keyword Glutamic-Acid Decarboxylase
Nod Mice
Peripheral Tolerance
B-Cells
Congenic Mice
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: ERA 2012 Admin Only
UQ Diamantina Institute - Open Access Collection
UQ Diamantina Institute Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 26 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 27 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Mon, 13 Feb 2012, 14:16:17 EST by System User on behalf of UQ Diamantina Institute