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J Exp Med. 2011 Sep 26;208(10):2043-53. doi: 10.1084/jem.20110767. Epub 2011 Aug 29.

Sustained suppression by Foxp3+ regulatory T cells is vital for infectious transplantation tolerance.

Author information

1
Sir William Dunn School of Pathology, Oxford University, Oxford OX1 3RE, England, UK.

Abstract

A paradigm shift in immunology has been the recent discovery of regulatory T cells (T reg cells), of which CD4(+)Foxp3(+) cells are proven as essential to self-tolerance. Using transgenic B6.Foxp3(hCD2) mice to isolate and ablate Foxp3(+) T reg cells with an anti-hCD2 antibody, we show for the first time that CD4(+)Foxp3(+) cells are crucial for infectious tolerance induced by nonablative anti-T cell antibodies. In tolerant animals, Foxp3(+) T reg cells are constantly required to suppress effector T cells still capable of causing tissue damage. Tolerated tissue contains T cells that are capable of rejecting it, but are prevented from doing so by therapeutically induced Foxp3(+) T reg cells. Finally, Foxp3(+) cells have been confirmed as the critical missing link through which infectious tolerance operates in vivo. Peripherally induced Foxp3(+) cells sustain tolerance by converting naive T cells into the next generation of Foxp3(+) cells. Empowering Foxp3(+) regulatory T cells in vivo offers a tractable route to avoid and correct tissue immunopathology.

PMID:
21875958
PMCID:
PMC3182049
DOI:
10.1084/jem.20110767
[Indexed for MEDLINE]
Free PMC Article
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