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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
2005-4-5
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pubmed:abstractText |
Although certain chemokines and their receptors guide homeostatic recirculation of T cells and others promote recruitment of activated T cells to inflammatory sites, little is known of the mechanisms underlying a third function, migration of Foxp3(+) regulatory T (T reg) cells to sites where they maintain unresponsiveness. We studied how T reg cells are recruited to cardiac allografts in recipients tolerized with CD154 monoclonal antibody (mAb) plus donor-specific transfusion (DST). Real-time polymerase chain reaction showed that intragraft Foxp3 levels in tolerized recipients were approximately 100-fold higher than rejecting allografts or allografts associated with other therapies inducing prolonged survival but not tolerance. Foxp3(+) cells were essential for tolerance because pretransplant thymectomy or peritransplant depletion of CD25(+) cells prevented long-term survival, as did CD25 mAb therapy in well-functioning allografts after CD154/DST therapy. Analysis of multiple chemokine pathways showed that tolerance was accompanied by intragraft up-regulation of CCR4 and one of its ligands, macrophage-derived chemokine (CCL22), and that tolerance induction could not be achieved in CCR4(-/-) recipients. We conclude that Foxp3 expression is specifically up-regulated within allografts of mice displaying donor-specific tolerance, that recruitment of Foxp3-expressing T reg cells to an allograft tissue is dependent on the chemokine receptor, CCR4, and that, in the absence of such recruitment, tolerizing strategies such as CD154 mAb therapy are ineffectual.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/15809349-10795741,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15809349-10811868,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15809349-11045999,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15809349-11429542,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15809349-11560999,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15809349-11812990,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15809349-12070291,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15809349-12522256,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15809349-12612578,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15809349-12658268,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15809349-12932350,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15809349-14617196,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15809349-14627918,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15809349-14662900,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15809349-14676299,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15809349-14707053,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15809349-14722622,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15809349-15014176,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15809349-15070759,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15809349-15128783,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15809349-15153467,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15809349-15322536,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15809349-7636184,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15809349-7678629,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15809349-7688139,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15809349-8943044,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15809349-9583862,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15809349-9846576,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15809349-9885918
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/Ccl22 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Ccr4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL22,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokines, CC,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Forkhead Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Foxp3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, CCR4,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Chemokine
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0022-1007
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
4
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pubmed:volume |
201
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1037-44
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:15809349-Animals,
pubmed-meshheading:15809349-Blotting, Western,
pubmed-meshheading:15809349-Cell Movement,
pubmed-meshheading:15809349-Chemokine CCL22,
pubmed-meshheading:15809349-Chemokines, CC,
pubmed-meshheading:15809349-DNA Primers,
pubmed-meshheading:15809349-DNA-Binding Proteins,
pubmed-meshheading:15809349-Flow Cytometry,
pubmed-meshheading:15809349-Forkhead Transcription Factors,
pubmed-meshheading:15809349-Heart Transplantation,
pubmed-meshheading:15809349-Immunohistochemistry,
pubmed-meshheading:15809349-Mice,
pubmed-meshheading:15809349-Mice, Inbred Strains,
pubmed-meshheading:15809349-Receptors, CCR4,
pubmed-meshheading:15809349-Receptors, Chemokine,
pubmed-meshheading:15809349-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:15809349-T-Lymphocytes,
pubmed-meshheading:15809349-Transplantation Tolerance,
pubmed-meshheading:15809349-Up-Regulation
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pubmed:year |
2005
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pubmed:articleTitle |
Recruitment of Foxp3+ T regulatory cells mediating allograft tolerance depends on the CCR4 chemokine receptor.
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pubmed:affiliation |
Department of Pathology and Laboratory Medicine, Joseph Stokes Jr. Research Institute and Biesecker Pediatric Liver Center, The Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA 19104, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, N.I.H., Extramural
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