title: Advantages of Foxp3(+) regulatory T cell depletion using DEREG mice.
abstract: Several mechanisms enable immunological self-tolerance. Regulatory T cells (Tregs) are a specialized T cell subset that prevents autoimmunity and excessive immune responses, but can also mediate detrimental tolerance to tumors and pathogens in a Foxp3-dependent manner. Genetic tools exploiting the foxp3 locus including bacterial artificial chromosome (BAC)-transgenic DEREG mice have provided essential information on Treg biology and the potential therapeutic modulation of tolerance. In DEREG mice, Foxp3(+) Tregs selectively express eGFP and diphtheria toxin (DT) receptor, allowing for the specific depletion of Tregs through DT administration. We here provide a detailed overview about important considerations such as DT toxicity, which affects any mouse strain treated with DT, and Treg rebound after depletion. Additionally, we point out the specific advantages of BAC-transgenic DEREG mice including their suitability to study organ-specific autoimmunity such as type I diabetes. Moreover, we discuss recent insights into the role of Tregs in viral infections. In summary, DEREG mice are an important tool to study Treg-mediated tolerance and its therapeutic circumvention.
authors.affiliation: Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture Between the Medical School Hannover and the Helmholtz Centre for Infection Research Feodor-Lynen-Str. 7, 30625, Hannover, Germany.
authors.forename: Christian T
authors.initials: CT
authors.lastname: Mayer
authors.affiliation: Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine Lane Building, Mailcode 5324, Stanford, CA, 94305, USA ; The Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System 3801 Miranda Avenue, Palo Alto, CA, 94304, USA.
authors.forename: Katharina
authors.initials: K
authors.lastname: Lahl
authors.affiliation: Experimental Immunology, Helmholtz Centre for Infection Research Inhoffenstr. 7, 38124, Braunschweig, Germany.
authors.forename: Pedro
authors.initials: P
authors.lastname: Milanez-Almeida
authors.affiliation: Molecular and Cellular Immunology/Immune Regulation, DFG-Center for Regenerative Therapies Dresden, Technische Universität Dresden Fetscherstr. 105, 01307, Dresden, Germany.
authors.forename: Deepika
authors.initials: D
authors.lastname: Watts
authors.affiliation: Institute for Virology, University Hospital Essen, University Duisburg-Essen Virchowstr.179, 45122, Essen, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Dittmer
authors.affiliation: Unit of Systems Toxicology, Finnish Institute of Occupational Health Topeliuksenkatu 41b, 00250, Helsinki, Finland.
authors.forename: Nanna
authors.initials: N
authors.lastname: Fyhrquist
authors.affiliation: Experimental Immunology, Helmholtz Centre for Infection Research Inhoffenstr. 7, 38124, Braunschweig, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Huehn
authors.affiliation: Institute for Molecular Health Sciences, Swiss Federal Institute of Technology Zuerich Otto-Stern-Weg 7, 8093, Zuerich, Switzerland.
authors.forename: Manfred
authors.initials: M
authors.lastname: Kopf
authors.affiliation: Molecular and Cellular Immunology/Immune Regulation, DFG-Center for Regenerative Therapies Dresden, Technische Universität Dresden Fetscherstr. 105, 01307, Dresden, Germany ; Paul Langerhans Institute Dresden, German Center for Diabetes Research (DZD) Fetscherstr. 74, 01307, Dresden, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Kretschmer
authors.affiliation: Department of Pathobiology, College of Veterinary Medicine, University of Tennessee Knoxville, TN, 37996, USA.
authors.forename: Barry
authors.initials: B
authors.lastname: Rouse
authors.affiliation: Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture Between the Medical School Hannover and the Helmholtz Centre for Infection Research Feodor-Lynen-Str. 7, 30625, Hannover, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Sparwasser
keywords: Autoimmunity; DEREG; Treg; diphtheria toxin (DT); regulatory T cells; tolerance