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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.

Original publication

DOI

10.1084/jem.20110767

Type

Journal article

Journal

The Journal of experimental medicine

Publication Date

09/2011

Volume

208

Pages

2043 - 2053

Addresses

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

Keywords

Animals, Mice, Inbred BALB C, Mice, Inbred CBA, Mice, Knockout, Mice, Homeodomain Proteins, Antibodies, Adoptive Transfer, Skin Transplantation, Self Tolerance, Transplantation Tolerance, Female, Male, T-Lymphocytes, Regulatory, Forkhead Transcription Factors