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

Authors
Journal
Journal of Experimental Medicine
0022-1007
Publisher
The Rockefeller University Press
Publication Date
Volume
208
Issue
10
Identifiers
DOI: 10.1084/jem.20110767
Keywords
  • Adoptive Transfer
  • Animals
  • Antibodies
  • Female
  • Forkhead Transcription Factors
  • Homeodomain Proteins
  • Male
  • Mice
  • Mice
  • Inbred Balb C
  • Mice
  • Inbred Cba
  • Mice
  • Knockout
  • Self Tolerance
  • Skin Transplantation
  • T-Lymphocytes
  • Regulatory
  • Transplantation Tolerance
Disciplines
  • Biology
  • Medicine

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.

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