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

KE Pauken, JL Linehan, JA Spanier… - The Journal of …, 2013 - journals.aai.org
KE Pauken, JL Linehan, JA Spanier, NL Sahli, LA Kalekar, BA Binstadt, JJ Moon, DL Mueller
The Journal of Immunology, 2013journals.aai.org
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 NOD and resistant B6 mice expressing IA g7. 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 …
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 NOD and resistant B6 mice expressing IA g7. 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 IA g7 were 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.
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