ArticleProceedings of the National Academy of Sciences of the United States of America1998
Widespread expression of an autoantigen-GAD65 transgene does not tolerize non-obese diabetic mice and can exacerbate disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1998. 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, 50 citations in OpenAlex.
- Type 1 diabetes pathogenesis and the role of inhibitory receptors in islet tolerance.Annals of the New York Academy of Sciences · 2020Review
- Article
- Regulation of GAD65 expression by SMAR1 and p53 upon Streptozotocin treatment.BMC molecular biology · 2012Article
- Antigen-specific therapeutic approaches in Type 1 diabetes.Cold Spring Harbor perspectives in medicine · 2012Review
- Article
- Article
- Glutamic acid decarboxylase-derived epitopes with specific domains expand CD4(+)CD25(+) regulatory T cells.PloS one · 2009Article
- Autoreactive human T-cell receptor initiates insulitis and impaired glucose tolerance in HLA DR4 transgenic mice.Journal of autoimmunity · 2008Article
- Prevention of type I diabetes transfer by glutamic acid decarboxylase 65 peptide 206-220-specific T cells.Proceedings of the National Academy of Sciences of the United States of America · 2004Article
- Dissecting autoimmune diabetes through genetic manipulation of non-obese diabetic mice.Diabetologia · 2003Review
- Evidence for a primary islet autoantigen (preproinsulin 1) for insulitis and diabetes in the nonobese diabetic mouse.Proceedings of the National Academy of Sciences of the United States of America · 2003Article
- Normal incidence of diabetes in NOD mice tolerant to glutamic acid decarboxylase.The Journal of experimental medicine · 2003Article
- CD4(+) T cells from glutamic acid decarboxylase (GAD)65-specific T cell receptor transgenic mice are not diabetogenic and can delay diabetes transfer.The Journal of experimental medicine · 2002Article
- Restricted islet-cell reactive T cell repertoire of early pancreatic islet infiltrates in NOD mice.Proceedings of the National Academy of Sciences of the United States of America · 2002Article
- Transgenic models of autoimmune disease.Clinical and experimental immunology · 2002Review
- Self-tolerance and the composition of T cell repertoire.Immunologic research · 2000Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
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Abstract
Glutamic acid decarboxylase (GAD)65 is a pancreatic beta cell autoantigen implicated as a target of T cells that initiate and sustain insulin-dependent diabetes mellitus (IDDM) in humans and in non-obese diabetic (NOD) mice. In an attempt to establish immunological tolerance toward GAD65 in NOD mice, and thereby to test the importance of GAD in IDDM, we generated three lines transgenic for murine GAD65 driven by a major histocompatibility complex class I promoter. However, despite widespread transgene expression in both newborn and adult mice, T cell tolerance was not induced. Mononuclear cell infiltration of the islets (insulitis) and diabetes were at least as bad in transgenic mice as in nontransgenic NOD mice, and in mice with the highest level of GAD65 expression, disease was exacerbated. In contrast, the same transgene introduced into mouse strain, FvB, induced neither insulitis nor diabetes, and T cells were tolerant to GAD. Thus, the failure of NOD mice to develop tolerance toward GAD65 reflects at minimum a basic defect in central tolerance, not seen in animals not predisposed to IDDM. Hence, it may not be possible experimentally to induce full tolerance toward GAD65 in prediabetic individuals. Additionally, the fact that autoimmune infiltration in GAD65 transgenic NOD mice remained largely restricted to the pancreas, indicates that the organ-specificity of autoimmune disease is dictated by tissue-specific factors in addition to those directing autoantigen expression.
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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.