title: T-bet Regulates Natural Regulatory T Cell Afferent Lymphatic Migration and Suppressive Function.
abstract: T-bet is essential for natural regulatory T cells (nTreg) to regulate Th1 inflammation, but whether T-bet controls other Treg functions after entering the inflammatory site is unknown. In an islet allograft model, T-bet(-/-) nTreg, but not induced Treg, failed to prolong graft survival as effectively as wild-type Treg. T-bet(-/-) nTreg had no functional deficiency in vitro but failed to home from the graft to draining lymph nodes (dLN) as efficiently as wild type. T-bet regulated expression of adhesion- and migration-related molecules, influencing nTreg distribution in tissues, so that T-bet(-/-) nTreg remained in the grafts rather than migrating to lymphatics and dLN. In contrast, both wild-type and T-bet(-/-) CD4(+) conventional T cells and induced Treg migrated normally toward afferent lymphatics. T-bet(-/-) nTreg displayed instability in the graft, failing to suppress Ag-specific CD4(+) T cells and prevent their infiltration into the graft and dLN. Thus, T-bet regulates nTreg migration into afferent lymphatics and dLN and consequently their suppressive stability in vivo.
authors.affiliation: Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD 21201;
authors.forename: Yanbao
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD 21201; Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201; and.
authors.forename: Sarwat
authors.identifier: http://orcid.org/0000-0001-6023-777X
authors.initials: S
authors.lastname: Ahmad
authors.affiliation: Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD 21201;
authors.forename: Daiki
authors.identifier: http://orcid.org/0000-0002-8274-848X
authors.initials: D
authors.lastname: Iwami
authors.affiliation: Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD 21201;
authors.forename: C Colin
authors.initials: CC
authors.lastname: Brinkman
authors.affiliation: Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD 21201; Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201; and Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201 jbromberg@smail.umaryland.edu.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Bromberg
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007108:Immune Tolerance / Q000276:immunology*; D016381:Islets of Langerhans Transplantation / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D042601:Lymphatic Vessels / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D060888:Real-Time Polymerase Chain Reaction; D020825:T-Box Domain Proteins / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D000098815:T-bet Transcription Factor
chemical_list: D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor