Linked Life Data

15809349

Source:http://linkedlifedata.com/resource/pubmed/id/15809349

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pubmed-article:15809349pubmed:abstractTextAlthough 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.lld:pubmed
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pubmed-article:15809349pubmed:authorpubmed-author:HancockWayne...lld:pubmed
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pubmed-article:15809349pubmed:authorpubmed-author:WangLiqingLlld:pubmed
pubmed-article:15809349pubmed:authorpubmed-author:LeeIrisIlld:pubmed
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pubmed-article:15809349pubmed:dateRevised2009-11-18lld:pubmed
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pubmed-article:15809349pubmed:articleTitleRecruitment of Foxp3+ T regulatory cells mediating allograft tolerance depends on the CCR4 chemokine receptor.lld:pubmed
pubmed-article:15809349pubmed:affiliationDepartment 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.lld:pubmed
pubmed-article:15809349pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:15809349pubmed:publicationTypeComparative Studylld:pubmed
pubmed-article:15809349pubmed:publicationTypeResearch Support, U.S. Gov't, P.H.S.lld:pubmed
pubmed-article:15809349pubmed:publicationTypeResearch Support, N.I.H., Extramurallld:pubmed