| Plasticity of human regulatory T cells in healthy subjects and patients with type 1 diabetes. | |
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MedLine Citation:
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PMID: 21368230 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Regulatory T cells (Tregs) constitute an attractive therapeutic target given their essential role in controlling autoimmunity. However, recent animal studies provide evidence for functional heterogeneity and lineage plasticity within the Treg compartment. To understand better the plasticity of human Tregs in the context of type 1 diabetes, we characterized an IFN-γ-competent subset of human CD4(+)CD127(lo/-)CD25(+) Tregs. We measured the frequency of Tregs in the peripheral blood of patients with type 1 diabetes by epigenetic analysis of the Treg-specific demethylated region (TSDR) and the frequency of the IFN-γ(+) subset by flow cytometry. Purified IFN-γ(+) Tregs were assessed for suppressive function, degree of TSDR demethylation, and expression of Treg lineage markers FOXP3 and Helios. The frequency of Tregs in peripheral blood was comparable but the FOXP3(+)IFN-γ(+) fraction was significantly increased in patients with type 1 diabetes compared to healthy controls. Purified IFN-γ(+) Tregs expressed FOXP3 and possessed suppressive activity but lacked Helios expression and were predominately methylated at the TSDR, characteristics of an adaptive Treg. Naive Tregs were capable of upregulating expression of Th1-associated T-bet, CXCR3, and IFN-γ in response to IL-12. Notably, naive, thymic-derived natural Tregs also demonstrated the capacity for Th1 differentiation without concomitant loss of Helios expression or TSDR demethylation. |
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Authors:
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Stephanie A McClymont; Amy L Putnam; Michael R Lee; Jonathan H Esensten; Weihong Liu; Maigan A Hulme; Ulrich Hoffmüller; Udo Baron; Sven Olek; Jeffrey A Bluestone; Todd M Brusko |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-03-02 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 186 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-03-22 Completed Date: 2011-06-16 Revised Date: 2012-05-07 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 3918-26 Citation Subset: AIM; IM |
Affiliation:
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Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Cell Proliferation* Cells, Cultured Child DNA Methylation Diabetes Mellitus, Type 1 / immunology*, pathology*, therapy Female Forkhead Transcription Factors / biosynthesis, genetics, metabolism Humans Inflammation Mediators / metabolism, physiology Interferon-gamma / biosynthesis*, physiology Lymphocyte Activation / immunology Male Middle Aged T-Lymphocyte Subsets / cytology, immunology, pathology T-Lymphocytes, Regulatory / cytology*, immunology*, pathology Young Adult |
| Grant Support | |
ID/Acronym/Agency:
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P01 AI035294-08/AI/NIAID NIH HHS; U19 AI056388-08/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/FOXP3 protein, human; 0/Forkhead Transcription Factors; 0/Inflammation Mediators; 82115-62-6/Interferon-gamma |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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