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rdf:type |
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lifeskim:mentions |
umls-concept:C0039194,
umls-concept:C0205217,
umls-concept:C0332307,
umls-concept:C0376249,
umls-concept:C0681850,
umls-concept:C1419119,
umls-concept:C1515655,
umls-concept:C1550501,
umls-concept:C1706203,
umls-concept:C2349001,
umls-concept:C2697811
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pubmed:issue |
1
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pubmed:dateCreated |
2004-7-6
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pubmed:abstractText |
Active T cell recognition of islet antigens has been postulated as the pathogenic mechanism in human type 1 diabetes, but evidence is scarce. If T cells are engaged, they are expected to display increased clonal size and exhibit a T helper (Th)1/Th2 differentiation state. We used a peptide library that covers tyrosine phosphatase IA-2, a target antigen expressed in pancreatic beta cells, to probe 8 diabetic patients and 5 HLA-matched controls. When tested in a high resolution IFNgamma/IL-4 double color ELISPOT assay directly ex vivo, the number of IA-2-reactive IFNgamma producing cells was 17-fold higher in patients than in controls and IL-4 producing cells were not present. An average of 9 peptides was recognized in the patients vs. one in the controls. Determinant recognition primarily involved CD4+ cells and showed high variability among the patients. Furthermore, anti-CD28 antibody signal enhances quantitative assessment of effector T cells in T1D patients. In vitro expansion with peptides and IL-2 results in detection of responding cells in the controls and loss of disease specificity of the T cell response. Together these data provide strong evidence for the active targeting of IA-2 by Th1 memory effector cells in human type 1 diabetes.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0896-8411
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pubmed:author |
pubmed-author:BoehmBernhard OBO,
pubmed-author:DittrichMarcus TMT,
pubmed-author:Durinovic-BellóIvanaI,
pubmed-author:KalbacherHubertH,
pubmed-author:KargesWolframW,
pubmed-author:KarulinAlexey YAY,
pubmed-author:LehmannPaul VPV,
pubmed-author:OttPatrick APA,
pubmed-author:QuastStefanS,
pubmed-author:Tary-LehmannMagdalenaM,
pubmed-author:Wünsche
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pubmed:copyrightInfo |
Copyright 2004 Elsevier Ltd.
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pubmed:issnType |
Print
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pubmed:volume |
23
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
45-54
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:15236752-Adult,
pubmed-meshheading:15236752-Autoantigens,
pubmed-meshheading:15236752-Diabetes Mellitus, Type 1,
pubmed-meshheading:15236752-Female,
pubmed-meshheading:15236752-Humans,
pubmed-meshheading:15236752-Interferon-gamma,
pubmed-meshheading:15236752-Interleukin-4,
pubmed-meshheading:15236752-Male,
pubmed-meshheading:15236752-Membrane Proteins,
pubmed-meshheading:15236752-Peptide Fragments,
pubmed-meshheading:15236752-Protein Tyrosine Phosphatase, Non-Receptor Type 1,
pubmed-meshheading:15236752-Protein Tyrosine Phosphatases,
pubmed-meshheading:15236752-Receptor-Like Protein Tyrosine Phosphatases, Class 8,
pubmed-meshheading:15236752-T-Lymphocyte Subsets,
pubmed-meshheading:15236752-T-Lymphocytes,
pubmed-meshheading:15236752-Th1 Cells
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pubmed:year |
2004
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pubmed:articleTitle |
Increased in vivo frequency of IA-2 peptide-reactive IFNgamma+/IL-4- T cells in type 1 diabetic subjects.
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pubmed:affiliation |
Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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