ArticleJournal of immunology (Baltimore, Md. : 1950)2010
Ins2 deficiency augments spontaneous HLA-A*0201-restricted T cell responses to insulin.
Article in Journal of immunology (Baltimore, Md. : 1950), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Humanized Mouse Models for Type 1 Diabetes.Current protocols · 2025Review
- Hydrogel-based approaches to target hypersensitivity mechanisms underlying autoimmune disease.Advanced drug delivery reviews · 2024Review
- Human insulin as both antigen and protector in type 1 diabetes.European journal of immunology · 2024Article
- Preclinical Models to Evaluate the Human Response to Autoantigen and Antigen-Specific Immunotherapy in Human Type 1 Diabetes.Frontiers in endocrinology · 2022Review
- Human stem cell derived beta-like cells engineered to present PD-L1 improve transplant survival in NOD mice carrying human HLA class I.Frontiers in endocrinology · 2022Article
- An Insulin-Inspired Supramolecular Hydrogel for Prevention of Type 1 Diabetes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- HLA-B*39:06 Efficiently Mediates Type 1 Diabetes in a Mouse Model Incorporating Reduced Thymic Insulin Expression.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Improved Murine MHC-Deficient HLA Transgenic NOD Mouse Models for Type 1 Diabetes Therapy Development.Diabetes · 2018Article
- Autoreactive T cells in type 1 diabetes.The Journal of clinical investigation · 2017Review
- An HLA-Transgenic Mouse Model of Type 1 Diabetes That Incorporates the Reduced but Not Abolished Thymic Insulin Expression Seen in Patients.Journal of diabetes research · 2016Article
- Compensatory mechanisms allow undersized anchor-deficient class I MHC ligands to mediate pathogenic autoreactive T cell responses.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Recognition of self and altered self by T cells in autoimmunity and allergy.Protein & cell · 2013Review
- Beyond HLA-A*0201: new HLA-transgenic nonobese diabetic mouse models of type 1 diabetes identify the insulin C-peptide as a rich source of CD8+ T cell epitopes.Journal of immunology (Baltimore, Md. : 1950) · 2012Article
- Animal models as tools to investigate antidiabetic and anti-inflammatory plants.Evidence-based complementary and alternative medicine : eCAM · 2012Article
- An update on the use of NOD mice to study autoimmune (Type 1) diabetes.Expert review of clinical immunology · 2010Article
- The anti-insulin trimolecular complex in type 1 diabetes.Current opinion in endocrinology, diabetes, and obesity · 2010Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
Abstract
Type 1 diabetes results from the autoimmune destruction of insulin-producing beta cells by T cells specific for beta cell Ags, including insulin. In humans, the non-MHC locus conferring the strongest disease susceptibility is the insulin gene, and alleles yielding lower thymic insulin expression are predisposing. We sought to incorporate this characteristic into an HLA-transgenic model of the disease and to determine the influence of reduced thymic insulin expression on CD8+ T cell responses to preproinsulin. We examined NOD.Ins2(-/-) mice, which do not express insulin in the thymus and show accelerated disease, to determine whether they exhibit quantitative or qualitative differences in CD8+ T cell responses to preproinsulin. We also generated NOD.Ins2(-/-) mice expressing type 1 diabetes-associated HLA-A*0201 (designated NOD.beta2m(-/-).HHD.Ins2(-/-)) in an effort to obtain an improved humanized disease model. We found that CD8+ T cell reactivity to certain insulin peptides was more readily detected in NOD.Ins2(-/-) mice than in NOD mice. Furthermore, the proportion of insulin-reactive CD8+ T cells infiltrating the islets of NOD.Ins2(-/-) mice was increased. NOD.beta2m(-/-).HHD.Ins2(-/-) mice exhibited rapid onset of disease and had an increased proportion of HLA-A*0201-restricted insulin-reactive T cells, including those targeting the clinically relevant epitope Ins B10-18. Our results suggest that insulin alleles that predispose to type 1 diabetes in humans do so, at least in part, by facilitating CD8+ T cell responses to the protein. We propose the NOD.beta2m(-/-).HHD.Ins2(-/-) strain as an improved humanized disease model, in particular for studies seeking to develop therapeutic strategies targeting insulin-specific T cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.