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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
45
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pubmed:dateCreated |
2009-11-11
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pubmed:abstractText |
Regulatory T cells (Tregs) can suppress a wide range of immune cells, making them an ideal candidate for the treatment of autoimmunity. The potential clinical translation of targeted therapy with antigen-specific Tregs is hampered by the difficulties of isolating rare specificities from the natural polyclonal T cell repertoire. Moreover, the initiating antigen is often unknown in autoimmune disease. Here we tested the ability of antigen-specific Tregs generated by retroviral gene transfer to ameliorate arthritis through linked suppression and therefore without cognate recognition of the disease-initiating antigen. We explored two distinct strategies: T cell receptor (TCR) gene transfer into purified CD4+CD25+ T cells was used to redirect the specificity of naturally occurring Tregs; and co-transfer of FoxP3 and TCR genes served to convert conventional CD4(+) T cells into antigen-specific regulators. Following adoptive transfer into recipient mice, the gene-modified T cells engrafted efficiently and retained TCR and FoxP3 expression. Using an established arthritis model, we demonstrate antigen-driven accumulation of the gene modified T cells at the site of joint inflammation, which resulted in a local reduction in the number of inflammatory Th17 cells and a significant decrease in arthritic bone destruction. Together, we describe a robust strategy to rapidly generate antigen-specific regulatory T cells capable of highly targeted inhibition of tissue damage in the absence of systemic immune suppression. This opens the possibility to target Tregs to tissue-specific antigens for the treatment of autoimmune tissue damage without the knowledge of the disease-causing autoantigens recognized by pathogenic T cells.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19884493-10323452,
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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 |
Nov
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pubmed:issn |
1091-6490
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
10
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pubmed:volume |
106
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
19078-83
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pubmed:dateRevised |
2010-9-28
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pubmed:meshHeading |
pubmed-meshheading:19884493-Adoptive Transfer,
pubmed-meshheading:19884493-Animals,
pubmed-meshheading:19884493-Arthritis, Rheumatoid,
pubmed-meshheading:19884493-Autoantigens,
pubmed-meshheading:19884493-Flow Cytometry,
pubmed-meshheading:19884493-Gene Transfer Techniques,
pubmed-meshheading:19884493-Genetic Vectors,
pubmed-meshheading:19884493-Immunotherapy, Adoptive,
pubmed-meshheading:19884493-Mice,
pubmed-meshheading:19884493-Mice, Inbred C57BL,
pubmed-meshheading:19884493-Retroviridae,
pubmed-meshheading:19884493-T-Cell Antigen Receptor Specificity,
pubmed-meshheading:19884493-T-Lymphocytes, Regulatory
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pubmed:year |
2009
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pubmed:articleTitle |
Adoptive therapy with redirected primary regulatory T cells results in antigen-specific suppression of arthritis.
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pubmed:affiliation |
Department of Immunology, University College London, Royal Free Hospital, London NW3 2PF, United Kingdom.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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