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

J exp med

Publication Date

26/09/2011

Volume

208

Pages

2043 - 2053

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