| Endogenous Expansion of Regulatory T Cells Leads to Long-Term Islet Graft Survival in Diabetic NOD Mice. | |
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MedLine Citation:
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PMID: 22299822 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Donor pancreatic lymph node cells (PLNC) protect islet transplants in Non-obese diabetic (NOD) mice. We hypothesized that induced FoxP3(+) regulatory T cells (Tregs) were required for long-term islet engraftment. NOD or NOD.NON mice were treated with ALS (antilymphocyte serum) and transplanted with NOR islets +/-PLNC (5 × 10(7) ). In vivo proliferation and expansion of FoxP3(+) Tregs was monitored in spleen and PLN from ALS- and ALS/PLNC-treated recipient mice. Anti-CD25 depletion was used to determine the necessity of Tregs for tolerance. FoxP3(+) numbers significantly increased in ALS/PLNC-treated recipients compared to ALS-treated mice. In ALS/PLNC-treated mice, recipient-derived Tregs localized to the transplanted islets, and this was associated with intact, insulin-producing β cells. Proliferation and expansion of FoxP3(+) Tregs was markedly increased in PLNC-treated mice with accepted islet grafts, but not in diabetic mice not receiving PLNC. Deletion of Tregs with anti-CD25 antibodies prevented islet graft tolerance and resulted in rejection. Adoptive transfer of Tregs to secondary NOD.scid recipients inhibited autoimmunity by cotransferred NOD effector T cells. Treg expansion induced by ALS/PLNC-treatment promoted long term islet graft survival. Strategies leading to Treg proliferation and localization to the transplant site represent a therapeutic approach to controlling recurrent autoimmunity. |
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Authors:
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Q Shi; J R Lees; D W Scott; D L Farber; S T Bartlett |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-2-2 |
Journal Detail:
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Title: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons Volume: - ISSN: 1600-6143 ISO Abbreviation: - Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-2-3 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100968638 Medline TA: Am J Transplant Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons. |
Affiliation:
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Division of Transplantation, Department of Surgery, University of Maryland School of Medicine, University of Maryland, Baltimore, MD. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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