Cutting edge: Type 1 diabetes occurs despite robust anergy among endogenous insulin-specific CD4 T cells in NOD mice

Kristen E. Pauken, Jonathan L. Linehan, Justin A. Spanier, Nathanael L. Sahli, Lokesh A. Kalekar, Bryce A. Binstadt, James J. Moon, Daniel L. Mueller, Marc K. Jenkins, Brian T. Fife

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Insulin-specific CD4+T cells are required for type 1 diabetes. How these cells are regulated and how tolerance breaks down are poorly understood because of a lack of reagents. Therefore, we used an enrichment method and tetramer reagents to track insulin-specific CD4+T cells in diabetes-susceptible NODand resistant B6 mice expressing I-Ag7. Insulin-specific cells were detected in both strains, but they only became activated, produced IFN-γ, and infiltrated the pancreas in NOD mice. Unexpectedly, the majority of Ag-experienced cells in NOD mice displayed an anergic phenotype, but this population decreased with age as tolerance was lost. B6 mice expressing I-Ag7were protected because insulin-specific cells did not become effector or anergic T cells but remained naive. These data suggest that NOD mice promote tolerance through anergy induction, but a small proportion of autoreactive T cells escape anergy to provoke type 1 diabetes.

Original languageEnglish (US)
Pages (from-to)4913-4917
Number of pages5
JournalJournal of Immunology
Volume191
Issue number10
DOIs
StatePublished - Nov 15 2013

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