Faculty Collaboration Database

A requisite role for induced regulatory T cells in tolerance based on expanding antigen receptor diversity. Immunity 2011 Jul 22;35(1):109-22

Date

07/05/2011

Pubmed ID

21723159

Pubmed Central ID

PMC3295638

DOI

10.1016/j.immuni.2011.03.029

Scopus ID

2-s2.0-79960453738 (requires institutional sign-in at Scopus site)   342 Citations

Abstract

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.

Author List

Haribhai D, Williams JB, Jia S, Nickerson D, Schmitt EG, Edwards B, Ziegelbauer J, Yassai M, Li SH, Relland LM, Wise PM, Chen A, Zheng YQ, Simpson PM, Gorski J, Salzman NH, Hessner MJ, Chatila TA, Williams CB

Authors

Martin J. Hessner PhD Professor in the Pediatrics department at Medical College of Wisconsin
Nita H. Salzman MD, PhD Director, Professor in the Pediatrics department at Medical College of Wisconsin
Pippa M. Simpson PhD Adjunct Professor in the Pediatrics department at Medical College of Wisconsin
Calvin B. Williams MD, PhD Chief, Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adoptive Transfer
Animals
Animals, Newborn
Autoimmunity
Cells, Cultured
Forkhead Transcription Factors
Immune Tolerance
Inflammation
Lymphocyte Depletion
Mice
Mice, Inbred BALB C
Mice, Mutant Strains
Mutation
Receptors, Antigen, T-Cell
T-Cell Antigen Receptor Specificity
T-Lymphocyte Subsets
T-Lymphocytes, Regulatory