Tracking Immunological Responses of Islet Antigen-Specific T Cells in the Nonobese Diabetic (NOD) Mouse Model of Type 1 Diabetes

2015 ◽  
pp. 127-134 ◽  
Author(s):  
Terri C. Thayer ◽  
F. Susan Wong
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Mouse Model ◽  
Nod Mouse ◽  
Immunological Responses ◽  
Nonobese Diabetic ◽  
Islet Antigen

scholarly journals Specificity and detection of insulin-reactive CD4+ T cells in type 1 diabetes in the nonobese diabetic (NOD) mouse

2011 ◽  
Vol 108 (40) ◽  
pp. 16729-16734 ◽  
Author(s):  
F. Crawford ◽  
B. Stadinski ◽  
N. Jin ◽  
A. Michels ◽  
M. Nakayama ◽  
...  
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Cd4 T Cells ◽  
Nod Mouse ◽  
Nonobese Diabetic

scholarly journals Thymically-derived Foxp3+ regulatory T cells are the primary regulators of type 1 diabetes in the non-obese diabetic mouse model

2019 ◽  
Author(s):  
Daniel R. Holohan ◽  
Frédéric Van Gool ◽  
Jeffrey A. Bluestone
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Regulatory T Cells ◽  
Mouse Model ◽  
Diabetic Mouse ◽  
Nod Mouse ◽  
Lymphoid Tissues ◽  
Functional Roles

AbstractRegulatory T cells (Tregs) are an immunosuppressive population that are identified based on the stable expression of the fate-determining transcription factor forkhead box P3 (Foxp3). Tregs can be divided into distinct subsets based on whether they developed in the thymus (tTregs) or in the periphery (pTregs). Whether there are unique functional roles that distinguish pTregs and tTregs remains largely unclear. To elucidate these functions, efforts have been made to specifically identify and modify individual Treg subsets. Deletion of the conserved non-coding sequence (CNS)1 in the Foxp3 locus leads to selective impairment of pTreg generation without disrupting tTreg generation in the C57BL/6J background. Using CRISPR-Cas9 genome editing technology, we removed the Foxp3 CNS1 region in the non-obese diabetic (NOD) mouse model of spontaneous type 1 diabetes mellitus (T1D) to determine if pTregs contribute to autoimmune regulation. Deletion of CNS1 impaired in vitro induction of Foxp3 in naïve NOD CD4+ T cells, but it did not alter Tregs in most lymphoid and non-lymphoid tissues analyzed except for the large intestine lamina propria, where a small but significant decrease in RORγt+ Tregs and corresponding increase in Helios+ Tregs was observed in NOD CNS1−/− mice. CNS1 deletion also did not alter the development of T1D or glucose tolerance despite increased pancreatic insulitis in pre-diabetic female NOD CNS1−/− mice. CNS1 Furthermore, the proportions of autoreactive Tregs and conventional T cells (Tconvs) within pancreatic islets were unchanged. These results suggest that pTregs dependent on the Foxp3 CNS1 region are not the dominant regulatory population controlling T1D in the NOD mouse model.

scholarly journals γδ T Cells Are Essential Effectors of Type 1 Diabetes in the Nonobese Diabetic Mouse Model

2013 ◽  
Vol 190 (11) ◽  
pp. 5392-5401 ◽  
Author(s):  
Janet G. M. Markle ◽  
Steve Mortin-Toth ◽  
Andrea S. L. Wong ◽  
Liping Geng ◽  
Adrian Hayday ◽  
...  
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Mouse Model ◽  
Γδ T Cells ◽  
Diabetic Mouse ◽  
Nonobese Diabetic Mouse ◽  
Nonobese Diabetic

scholarly journals Thioreductase-Containing Epitopes Inhibit the Development of Type 1 Diabetes in the NOD Mouse Model

2016 ◽  
Vol 7 ◽  
Author(s):  
Elin Malek Abrahimians ◽  
Luc Vander Elst ◽  
Vincent A. Carlier ◽  
Jean-Marie Saint-Remy
Keyword(s):  
Type 1 Diabetes ◽  
Mouse Model ◽  
Nod Mouse

scholarly journals Increased islet antigen–specific regulatory and effector CD4+ T cells in healthy individuals with the type 1 diabetes–protective haplotype

2020 ◽  
Vol 5 (44) ◽  
pp. eaax8767 ◽  
Author(s):  
Xiaomin Wen ◽  
Junbao Yang ◽  
Eddie James ◽  
I-Ting Chow ◽  
Helena Reijonen ◽  
...  
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
T Cell ◽  
Regulatory T Cells ◽  
Interleukin 4 ◽  
Specific Class ◽  
Protective Haplotype ◽  
Specific Effector ◽  
Islet Antigen

The DRB1*15:01-DQB1*06:02 (DR1501-DQ6) haplotype is linked to dominant protection from type 1 diabetes, but the cellular mechanism for this association is unclear. To address this question, we identified multiple DR1501- and DQ6-restricted glutamate decarboxylase 65 (GAD65) and islet-specific glucose-6-phosphatase catalytic subunit–related protein (IGRP)–specific T cell epitopes. Three of the DR1501/DQ6-restricted epitopes identified were previously reported to be restricted by DRB1*04:01/DRB1*03:01/DQB1*03:02. We also used specific class II tetramer reagents to assess T cell frequencies. Our results indicated that GAD65- and IGRP-specific effector and CD25+CD127−FOXP3+ regulatory CD4+ T cells were present at higher frequencies in individuals with the protective haplotype than those with susceptible or neutral haplotypes. We further confirmed higher frequencies of islet antigen–specific effector and regulatory CD4+ T cells in DR1501-DQ6 individuals through a CD154/CD137 up-regulation assay. DR1501-restricted effector T cells were capable of producing interferon-γ (IFN-γ) and interleukin-4 (IL-4) but were more likely to produce IL-10 compared with effectors from individuals with susceptible haplotypes. To evaluate their capacity for antigen-specific regulatory activity, we cloned GAD65 and IGRP epitope–specific regulatory T cells. We showed that these regulatory T cells suppressed DR1501-restricted GAD65- and IGRP-specific effectors and DQB1*03:02-restricted GAD65-specific effectors in an antigen-specific fashion. In total, these results suggest that the protective DR1501-DQ6 haplotype confers protection through increased frequencies of islet-specific IL-10–producing T effectors and CD25+CD127−FOXP3+ regulatory T cells.

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