Send to

Choose Destination
Immunity. 2011 Jul 22;35(1):109-22. doi: 10.1016/j.immuni.2011.03.029. Epub 2011 Jun 30.

A requisite role for induced regulatory T cells in tolerance based on expanding antigen receptor diversity.

Author information

Section of Rheumatology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA.


Although both natural and induced regulatory T (nTreg and iTreg) cells can enforce tolerance, the mechanisms underlying their synergistic actions have not been established. We examined the functions of nTreg and iTreg cells by adoptive transfer immunotherapy of newborn Foxp3-deficient mice. As monotherapy, only nTreg cells prevented disease lethality, but did not suppress chronic inflammation and autoimmunity. Provision of Foxp3-sufficient conventional T cells with nTreg cells reconstituted the iTreg pool and established tolerance. In turn, acute depletion of iTreg cells in rescued mice resulted in weight loss and inflammation. Whereas the transcriptional signatures of nTreg and in vivo-derived iTreg cells were closely matched, there was minimal overlap in their T cell receptor (TCR) repertoires. Thus, iTreg cells are an essential nonredundant regulatory subset that supplements nTreg cells, in part by expanding TCR diversity within regulatory responses.

[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Secondary source ID, Grant support

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center