| Identification and expansion of highly suppressive CD8+FoxP3+ regulatory T cells after experimental allogeneic bone marrow transplantation. | |
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MedLine Citation:
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PMID: 22538855 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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FoxP3(+) confers suppressive properties and is confined to regulatory T cells (T(reg)) that potently inhibit autoreactive immune responses. In the transplant setting natural CD4(+) T(reg) are critical in controlling alloreactivity and the establishment of tolerance. We now identify an important CD8(+) population of FoxP3(+) T(reg) that convert from CD8(+) conventional donor T cells after allogeneic but not syngeneic bone marrow transplantation (BMT). These CD8(+) T(reg) undergo conversion in the mesenteric lymph nodes under the influence of recipient dendritic cells and TGFβ. Importantly, this population is as important for protection from GVHD as the well-studied natural CD4(+)FoxP3(+) population and are more potent in exerting class-I restricted and antigen-specific suppression in vitro and in vivo. Critically, CD8(+)FoxP3(+) T(reg) are exquisitely sensitive to inhibition by cyclosporine but can be massively and specifically expanded in vivo to prevent GVHD by co-administering Rapamycin and IL-2 antibody complexes. CD8(+)FoxP3(+) T(reg) thus represent a new regulatory population with considerable potential to preferentially subvert MHC class-I restricted T cell responses following BMT. |
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Authors:
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Renee J Robb; Katie E Lineburg; Rachel D Kuns; Yana A Wilson; Neil C Raffelt; Stuart D Olver; Antiopi Varelias; Kylie A Alexander; Bianca E Teal; Tim Sparwasser; Gunter J Hammerling; Kate A Markey; Motoko Koyama; Andrew D Clouston; Christian R Engwerda; Geoffrey R Hill; Kelli P A Macdonald |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-4-26 |
Journal Detail:
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Title: Blood Volume: - ISSN: 1528-0020 ISO Abbreviation: - Publication Date: 2012 Apr |
Date Detail:
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Created Date: 2012-4-27 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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The Bone Marrow Transplantation Laboratory, Queensland Institute of Medical Research, Brisbane, QLD, Australia; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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