Blockade of chronic graft-versus-host disease by alloantigen-induced CD4+CD25+Foxp3+ regulatory T cells in nonlymphopenic hosts.

Blockade of chronic graft-versus-host disease by alloantigen-induced CD4+CD25+Foxp3+ regulatory T cells in nonlymphopenic hosts. Research Abstract Details 

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Blockade of chronic graft-versus-host disease by alloantigen-induced CD4+CD25+Foxp3+ regulatory T cells in nonlymphopenic hosts. Abstract Text:

A Giorgini,A Noble,A Giorgini,A Noble,

CD4(+)CD25(+) regulatory T cells (Tregs) are well known to suppress immunopathology induced in lymphopenic animals following T cell reconstitution, including acute graft-versus-host disease (GVHD) post-bone marrow transplantation. The regulatory potential of this subset in nonlymphopenic hosts and in chronic, Th2-mediated GVHD is less clear. We have generated alloantigen-specific cells from CD4(+)CD25(+) populations stimulated with MHC-disparate dendritic cells and found them to express a stable Treg forkhead box p3(+) phenotype with enhanced suppressive activity mediated by cell contact. When transferred into nonlymphopenic F1 hosts, nonspecific Tregs proliferated as rapidly as CD4(+)CD25(-) cells but displayed distinct growth kinetics in vitro. Tregs, expanded in response to alloantigen in vitro, displayed greatly enhanced suppressive activity, which was partially antigen-specific. They were effective inhibitors of chronic GVHD, blocking donor cell engraftment, splenomegaly, autoantibody production, and glomerulonephritis. CD25(+) and CD25(-) cells were equally susceptible to inhibition by immunosuppressive drugs targeting TCR signaling and rapamycin, but Tregs were resistant to inhibition by dexamethasone. The data indicate that alloantigen-driven expansion, rather than homeostatic proliferation, is key to the effectiveness of CD4(+)CD25(+) Tregs in GVHD and suggest that cellular therapy with alloantigen-induced Tregs in combination with glucocorticoid treatment would be effective in prevention of chronic GVHD after immune reconstitution.

Blockade of chronic graft-versus-host disease by alloantigen-induced CD4+CD25+Foxp3+ regulatory T cells in nonlymphopenic hosts. Publishing Authors By Initials

A Giorgini,A Noble,A Giorgini,A Noble,

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Blockade of chronic graft-versus-host disease by alloantigen-induced CD4+CD25+Foxp3+ regulatory T cells in nonlymphopenic hosts. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of leukocyte biology

VOLUME: 82

Page Numbers: 1053-61

Journal Abbreviation: J. Leukoc. Biol.

ISSN: 0741-5400

DAY: 7

MONTH: 08

YEAR: 2007

Blockade of chronic graft-versus-host disease by alloantigen-induced CD4+CD25+Foxp3+ regulatory T cells in nonlymphopenic hosts. Information

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LANGUAGE: eng

NlmUniqueID: 8405628

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AFFILIATION: Allergy, and Respiratory Science, King's College London, 5th Floor Thomas Guy House, Guy's Hospital Campus, London, UK.

Country: United States

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MEDLINETA: J Leukoc Biol

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