| Demonstration of islet-autoreactive CD8 T cells in insulitic lesions from recent onset and long-term type 1 diabetes patients. | |
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MedLine Citation:
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PMID: 22213807 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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A direct association of islet-autoreactive T cells with β cell destruction in human pancreatic islets from type 1 diabetes (T1D) patients has never been demonstrated, and little is known about disease progression after diagnosis. Frozen pancreas samples were obtained from 45 cadaveric T1D donors with disease durations ranging from 1 wk to >50 yr, 14 nondiabetic controls, 5 nondiabetics with islet autoantibodies, 2 cases of gestational diabetes, and 6 T2D patients. Sections were systematically analyzed for the presence of insulin-sufficient β cells, CD8(+) insulitic lesions, and HLA class I hyperexpression. Finally, consecutive sections from HLA-A2-expressing individuals were probed for CD8 T cell reactivity against six defined islet autoantigens associated with T1D by in situ tetramer staining. Both single and multiple CD8 T cell autoreactivities were detected within individual islets in a subset of patients up to 8 yr after clinical diagnosis. Pathological features such as HLA class I hyperexpression and insulitis were specific for T1D and persisted in a small portion of the patients with longstanding disease. Insulitic lesions consistently presented in a multifocal pattern with varying degrees of infiltration and β cell loss across affected organs. Our observations provide the first direct proof for islet autoreactivity within human islets and underscore the heterogeneous and chronic disease course. |
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Authors:
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Ken T Coppieters; Francesco Dotta; Natalie Amirian; Peter D Campbell; Thomas W H Kay; Mark A Atkinson; Bart O Roep; Matthias G von Herrath |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-3 |
Journal Detail:
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Title: The Journal of experimental medicine Volume: - ISSN: 1540-9538 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-4 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985109R Medline TA: J Exp Med Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Type 1 Diabetes Center, the La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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