title: Affinity for self antigen selects Treg cells with distinct functional properties.
abstract: The manner in which regulatory T cells (Treg cells) control lymphocyte homeostasis is not fully understood. We identified two Treg cell populations with differing degrees of self-reactivity and distinct regulatory functions. We found that GITR(hi)PD-1(hi)CD25(hi) (Triple(hi)) Treg cells were highly self-reactive and controlled lympho-proliferation in peripheral lymph nodes. GITR(lo)PD-1(lo)CD25(lo) (Triple(lo)) Treg cells were less self-reactive and limited the development of colitis by promoting the conversion of CD4(+) Tconv cells into induced Treg cells (iTreg cells). Although Foxp3-deficient (Scurfy) mice lacked Treg cells, they contained Triple(hi)-like and Triple(lo)-like CD4(+) T cells zsuper> T cells infiltrated the skin, whereas Scurfy Triple(lo)CD4(+) T cells induced colitis and wasting disease. These findings indicate that the affinity of the T cell antigen receptor for self antigen drives the differentiation of Treg cells into distinct subsets with non-overlapping regulatory activities.
authors.affiliation: Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland.|Department of Nephrology, University Hospital Basel and University of Basel, Basel, Switzerland.
authors.forename: Lena
authors.initials: L
authors.lastname: Wyss
authors.affiliation: Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Stadinski
authors.affiliation: Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland.
authors.forename: Carolyn G
authors.initials: CG
authors.lastname: King
authors.affiliation: Molecular and Cellular Immunology/Immune Regulation, DFG-Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany.
authors.forename: Sonja
authors.identifier: 0000-0002-5040-6426
authors.initials: S
authors.lastname: Schallenberg
authors.affiliation: MRC Centre for Immune Regulation, Institute for Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
authors.forename: Nicholas I
authors.initials: NI
authors.lastname: McCarthy
authors.affiliation: Academy of Immunology and Microbiology, Institute for Basic Science, Pohang, Republic of Korea.|Department of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea.
authors.forename: Jun Young
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Molecular and Cellular Immunology/Immune Regulation, DFG-Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany.|Paul Langerhans Institute Dresden, German Center for Diabetes Research (DZD), Dresden, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Kretschmer
authors.affiliation: Institute of Pathology, Molecular Pathology Division, University Hospital of Basel, Basel, Switzerland.
authors.forename: Luigi M
authors.initials: LM
authors.lastname: Terracciano
authors.affiliation: MRC Centre for Immune Regulation, Institute for Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
authors.forename: Graham
authors.initials: G
authors.lastname: Anderson
authors.affiliation: Academy of Immunology and Microbiology, Institute for Basic Science, Pohang, Republic of Korea.|Department of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea.|Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
authors.forename: Charles D
authors.initials: CD
authors.lastname: Surh
authors.affiliation: Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Eric S
authors.initials: ES
authors.lastname: Huseby
authors.affiliation: Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland.|Department of Nephrology, University Hospital Basel and University of Basel, Basel, Switzerland.
authors.forename: Ed
authors.initials: E
authors.lastname: Palmer
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D060966:Clonal Selection, Antigen-Mediated; D003092:Colitis / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D053450:Glucocorticoid-Induced TNFR-Related Protein / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D037182:T-Cell Antigen Receptor Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000637:transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000637:transplantation; D019282:Wasting Syndrome / Q000276:immunology*
chemical_list: D001324:Autoantigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053450:Glucocorticoid-Induced TNFR-Related Protein; D011948:Receptors, Antigen, T-Cell; C106544:Tnfrsf18 protein, mouse