| Expression level of a pancreatic neo-antigen in beta cells determines degree of diabetes pathogenesis. | |
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MedLine Citation:
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PMID: 20932718 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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It is not fully understood how the expression level of autoantigens in beta cells impacts autoimmune diabetes (T1D) development. Earlier studies using ovalbumin and also insulin had shown that secreted antigens could enhance diabetes development through facilitated presentation by antigen presenting cells. Here we sought to determine how the expression level of a membrane bound, non-secreted or cross-presented neo-antigen, the glycoprotein (GP) of lymphocytic choriomeningitis virus (LCMV), would influence T1D. We found that an RIP-LCMV transgenic mouse line exhibiting higher levels of beta cell GP expression developed more severe diabetes after LCMV infection or transfer of high numbers of activated autoreactive T cells. Importantly, all beta cells were lost and a significant increase in morbidity and mortality from T1D was noted. Insulitis and accumulation of autoaggressive CD8 cells was more profound in the RIP-LCMV-GP high-expressor line. Interestingly, the additional introduction of neo-antigen-specific CD4(+) helper or regulatory T cells was able to influence diabetogenesis positively or negatively. We conclude that a higher degree of autoantigen expression results in increased diabetes susceptibility. Therefore, autoantigens such as insulin that are expressed at higher levels in beta cells might have a more profound impact on diabetes pathogenesis. |
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Authors:
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Marianne M Martinic; Christoph Huber; Ken Coppieters; Janine E Oldham; Amanda L Gavin; Matthias G von Herrath |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-10-06 |
Journal Detail:
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Title: Journal of autoimmunity Volume: 35 ISSN: 1095-9157 ISO Abbreviation: J. Autoimmun. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-10-25 Completed Date: 2011-05-23 Revised Date: 2011-12-21 |
Medline Journal Info:
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Nlm Unique ID: 8812164 Medline TA: J Autoimmun Country: England |
Other Details:
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Languages: eng Pagination: 404-13 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Ltd. All rights reserved. |
Affiliation:
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Type 1 Diabetes Center at the La Jolla Institute for Allergy & Immunology, La Jolla, CA 92037, USA. mariannemartinic@yahoo.de |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adoptive Transfer Animals Antigens, Viral / biosynthesis, genetics Arenaviridae Infections / genetics, immunology*, physiopathology Autoantigens / biosynthesis, genetics CD8-Positive T-Lymphocytes / immunology, metabolism*, pathology, transplantation Cells, Cultured Cross-Priming / genetics Cytotoxicity, Immunologic / genetics Diabetes Mellitus, Type 1 / genetics, immunology*, physiopathology Disease Progression Glycoproteins / biosynthesis, genetics Insulin-Secreting Cells / metabolism*, pathology Lymphocyte Activation / genetics Lymphocytic choriomeningitis virus / pathogenicity, physiology* Mice Mice, Transgenic Receptors, Antigen, T-Cell / genetics |
| Grant Support | |
ID/Acronym/Agency:
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A1067403//PHS HHS; DK78013/DK/NIDDK NIH HHS; P01 AI058105-01/AI/NIAID NIH HHS; P01 AI058105-010001/AI/NIAID NIH HHS; P01 AI058105-02/AI/NIAID NIH HHS; P01 AI058105-020001/AI/NIAID NIH HHS; P01 AI058105-03/AI/NIAID NIH HHS; P01 AI058105-030001/AI/NIAID NIH HHS; P01 AI058105-04/AI/NIAID NIH HHS; P01 AI058105-040001/AI/NIAID NIH HHS; P01 AI058105-05/AI/NIAID NIH HHS; P01 AI058105-050001/AI/NIAID NIH HHS; P01 AI058105-05S1/AI/NIAID NIH HHS; P01 AI058105-05S10001/AI/NIAID NIH HHS; P01 AI58105/AI/NIAID NIH HHS; R01 AI067403-01A2/AI/NIAID NIH HHS; R01 AI067403-02/AI/NIAID NIH HHS; R01 AI067403-03/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, Viral; 0/Autoantigens; 0/Glycoproteins; 0/Receptors, Antigen, T-Cell |
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