title: Cutting edge: type 1 diabetes occurs despite robust anergy among endogenous insulin-specific CD4 T cells in NOD mice.
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 I-A(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 I-A(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.
authors.affiliation: Center for Immunology, University of Minnesota, Minneapolis, MN 55455;
authors.forename: Kristen E
authors.initials: KE
authors.lastname: Pauken
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Linehan
authors.forename: Justin A
authors.initials: JA
authors.lastname: Spanier
authors.forename: Nathanael L
authors.initials: NL
authors.lastname: Sahli
authors.forename: Lokesh A
authors.initials: LA
authors.lastname: Kalekar
authors.forename: Bryce A
authors.initials: BA
authors.lastname: Binstadt
authors.forename: James J
authors.initials: JJ
authors.lastname: Moon
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Mueller
authors.forename: Marc K
authors.initials: MK
authors.lastname: Jenkins
authors.forename: Brian T
authors.initials: BT
authors.lastname: Fife
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D017635:Clonal Anergy / Q000276:immunology*; D003921:Diabetes Mellitus, Experimental / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D007328:Insulin / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D010179:Pancreas / Q000166:cytology / Q000276:immunology
chemical_list: D007328:Insulin; D007371:Interferon-gamma