title: Identification and characterization of latency-associated peptide-expressing γδ T cells.
abstract: γδ T cells are a subset of lymphocytes specialized in protecting the host against pathogens and tumours. Here we describe a subset of regulatory γδ T cells that express the latency-associated peptide (LAP), a membrane-bound TGF-β1. Thymic CD27+IFN-γ+CCR9+α4β7+TCRγδ+ cells migrate to the periphery, particularly to Peyer's patches and small intestine lamina propria, where they upregulate LAP, downregulate IFN-γ via ATF-3 expression and acquire a regulatory phenotype. TCRγδ+LAP+ cells express antigen presentation molecules and function as antigen presenting cells that induce CD4+Foxp3+ regulatory T cells, although TCRγδ+LAP+ cells do not themselves express Foxp3. Identification of TCRγδ+LAP+ regulatory cells provides an avenue for understanding immune regulation and biologic processes linked to intestinal function and disease.
authors.affiliation: Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Rafael M
authors.initials: RM
authors.lastname: Rezende
authors.affiliation: Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Andre P
authors.initials: AP
authors.lastname: da Cunha
authors.affiliation: Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Chantal
authors.initials: C
authors.lastname: Kuhn
authors.affiliation: Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Rubino
authors.affiliation: Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.|Rheumatology Unit, Department of Medicine at Karolinska University Hospital, Karolinska Institute, Solna, Stockholm 17177, Sweden.
authors.forename: Hanane
authors.initials: H
authors.lastname: M'Hamdi
authors.affiliation: Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Galina
authors.initials: G
authors.lastname: Gabriely
authors.affiliation: Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Tyler
authors.initials: T
authors.lastname: Vandeventer
authors.affiliation: Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Shirong
authors.initials: S
authors.lastname: Liu
authors.affiliation: Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Ron
authors.initials: R
authors.lastname: Cialic
authors.affiliation: Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31.270-901, Brazil.
authors.forename: Natalia
authors.initials: N
authors.lastname: Pinheiro-Rosa
authors.affiliation: Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31.270-901, Brazil.
authors.forename: Rafael P
authors.initials: RP
authors.lastname: Oliveira
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.|Department of Physics, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Jellert T
authors.initials: JT
authors.lastname: Gaublomme
authors.affiliation: Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Obholzer
authors.affiliation: Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: James
authors.initials: J
authors.lastname: Kozubek
authors.affiliation: Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.|Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, Massachusetts 02142, USA.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Pochet
authors.affiliation: Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31.270-901, Brazil.
authors.forename: Ana M C
authors.initials: AMC
authors.lastname: Faria
authors.affiliation: Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Howard L
authors.initials: HL
authors.lastname: Weiner
mesh_terms: D051700:Activating Transcription Factor 3 / Q000235:genetics / Q000276:immunology; D000328:Adult; D000818:Animals; D020296:Animals, Congenic; D000938:Antigen-Presenting Cells; D003092:Colitis / Q000276:immunology*; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma; D007413:Intestinal Mucosa / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D010581:Peyer's Patches / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000276:immunology*
chemical_list: D051700:Activating Transcription Factor 3; C103002:Atf3 protein, mouse; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta; D053773:Transforming Growth Factor beta1; D007371:Interferon-gamma