| Cellular Mechanisms of Restored β-Cell Tolerance Mediated by Protective Alleles of Idd3 and Idd5. | |
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MedLine Citation:
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PMID: 22106155 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Type 1 diabetes genes within the IL-2, CTLA-4, and NRAMP1 pathways influence development of autoimmune diabetes in humans and NOD mice. In NOD mice, when present together, protective alleles encoding interleukin-2 (IL-2), Idd3 candidate gene, CTLA-4, NRAMP1, and ACADL (candidate genes for the Idd5.1, Idd5.2, and Idd5.3 subregions) provide nearly complete diabetes protection. To define where the protective alleles of Idd3 and the Idd5 subregions must be present to protect from diabetes and tolerize islet-specific CD8(+) T cells, SCID mice were reconstituted so that the host and lymphocytes expressed various combinations of protective and susceptibility alleles at Idd3 and Idd5. Although protective Idd3 alleles in the lymphocytes and protective Idd5 alleles in the SCID host contributed most significantly to CD8 tolerance, both were required together in both lymphocyte and nonlymphocyte cells to recapitulate the potent diabetes protection observed in intact Idd3/5 mice. We conclude that genetic regions involved in autoimmune disease are not restricted in their influence to individual cell types. Even a single protective gene product, such as IL-2, must be expressed in both the lymphocytes and dendritic cells to exert its full extent of disease protection. These studies highlight the pleiotropic effects of genes that determine autoimmune disease susceptibility. |
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Authors:
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Emma E Hamilton-Williams; Jocelyn Cheung; Daniel B Rainbow; Kara M Hunter; Linda S Wicker; Linda A Sherman |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-21 |
Journal Detail:
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Title: Diabetes Volume: - ISSN: 1939-327X ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-22 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372763 Medline TA: Diabetes Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Immunology and Microbial Sciences, The Scripps Research Institute, La Jolla, California. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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