| Cutting edge: mechanisms of IL-2-dependent maintenance of functional regulatory T cells. | |
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MedLine Citation:
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PMID: 21037099 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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IL-2 controls the survival of regulatory T cells (Tregs), but it is unclear whether IL-2 also directly affects Treg suppressive capacity in vivo. We have found that eliminating Bim-dependent apoptosis in IL-2- and CD25-deficient mice restored Treg numbers but failed to cure their lethal autoimmune disease, demonstrating that IL-2-dependent survival and suppressive activity can be uncoupled in Tregs. Treatment with IL-2-anti-IL-2-Ab complexes enhanced the numbers and suppressive capacity of IL-2-deprived Tregs with striking increases in CD25, CTLA-4, and CD39/CD73 expression. Although cytokine treatment induced these suppressive mechanisms in both IL-2(-/-) and IL-2(-/-)Bim(-/-) mice, it only reversed autoimmune disease in the latter. Our results suggest that successful IL-2 therapy of established autoimmune diseases will require a threshold quantity of Tregs present at the start of treatment and show that the suppressive capacity of Tregs critically depends on IL-2 even when Treg survival is independent of this cytokine. |
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Authors:
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Luke Barron; Hans Dooms; Katrina K Hoyer; Wilson Kuswanto; Jerry Hofmann; William E O'Gorman; Abul K Abbas |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-10-29 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 185 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-18 Completed Date: 2011-01-10 Revised Date: 2011-12-21 |
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: 6426-30 Citation Subset: AIM; IM |
Affiliation:
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Department of Pathology, University of California San Francisco, San Francisco, CA 94143-0506, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Anemia, Hemolytic, Autoimmune
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genetics,
immunology,
therapy Animals Apoptosis Regulatory Proteins / deficiency, genetics Cell Proliferation Cells, Cultured Coculture Techniques Forkhead Transcription Factors / deficiency, genetics Gene Deletion Interleukin-2 / genetics, physiology* Interleukin-2 Receptor alpha Subunit / deficiency, genetics Membrane Proteins / deficiency, genetics Mice Mice, Inbred BALB C Mice, Knockout Mice, Transgenic Proto-Oncogene Proteins / deficiency, genetics T-Lymphocytes, Regulatory / immunology*, metabolism*, pathology |
| Grant Support | |
ID/Acronym/Agency:
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P01 AI035297-19/AI/NIAID NIH HHS; P01 AI35297/AI/NIAID NIH HHS; R01 AI073656/AI/NIAID NIH HHS; R01 AI073656-04/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Apoptosis Regulatory Proteins; 0/Bcl-2-like protein 11; 0/Forkhead Transcription Factors; 0/Foxp3 protein, mouse; 0/IL2 protein, human; 0/Interleukin-2; 0/Interleukin-2 Receptor alpha Subunit; 0/Membrane Proteins; 0/Proto-Oncogene Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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