title: A requisite role for induced regulatory T cells in tolerance based on expanding antigen receptor diversity.
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.
authors: Section of Rheumatology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors: Dipica
authors: D
authors: Haribhai
authors: Jason B
authors: JB
authors: Williams
authors: Shuang
authors: S
authors: Jia
authors: Derek
authors: D
authors: Nickerson
authors: Erica G
authors: EG
authors: Schmitt
authors: Brandon
authors: B
authors: Edwards
authors: Jennifer
authors: J
authors: Ziegelbauer
authors: Maryam
authors: M
authors: Yassai
authors: Shun-Hwa
authors: SH
authors: Li
authors: Lance M
authors: LM
authors: Relland
authors: Petra M
authors: PM
authors: Wise
authors: Andrew
authors: A
authors: Chen
authors: Yu-Qian
authors: YQ
authors: Zheng
authors: Pippa M
authors: PM
authors: Simpson
authors: Jack
authors: J
authors: Gorski
authors: Nita H
authors: NH
authors: Salzman
authors: Martin J
authors: MJ
authors: Hessner
authors: Talal A
authors: TA
authors: Chatila
authors: Calvin B
authors: CB
authors: Williams
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000831:Animals, Newborn; D015551:Autoimmunity / Q000235:genetics; D002478:Cells, Cultured; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D007108:Immune Tolerance; D007249:Inflammation; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D009154:Mutation / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D037182:T-Cell Antigen Receptor Specificity / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D011948:Receptors, Antigen, T-Cell