Advantages of Foxp3(+) regulatory T cell depletion using DEREG mice.

Mayer CT; Lahl K; Milanez-Almeida P; Watts D; Dittmer U; Fyhrquist N; Huehn J; Kopf M; Kretschmer K; Rouse B; Sparwasser T

doi:10.1002/iid3.33

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Journal article

Advantages of Foxp3(+) regulatory T cell depletion using DEREG mice.

Mayer CT 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.
Lahl K 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.
Milanez-Almeida P Experimental Immunology, Helmholtz Centre for Infection Research Inhoffenstr. 7, 38124, Braunschweig, Germany.
Watts D Molecular and Cellular Immunology/Immune Regulation, DFG-Center for Regenerative Therapies Dresden, Technische Universität Dresden Fetscherstr. 105, 01307, Dresden, Germany.
Dittmer U Institute for Virology, University Hospital Essen, University Duisburg-Essen Virchowstr.179, 45122, Essen, Germany.
Fyhrquist N Unit of Systems Toxicology, Finnish Institute of Occupational Health Topeliuksenkatu 41b, 00250, Helsinki, Finland.
Huehn J Experimental Immunology, Helmholtz Centre for Infection Research Inhoffenstr. 7, 38124, Braunschweig, Germany.
Kopf M Institute for Molecular Health Sciences, Swiss Federal Institute of Technology Zuerich Otto-Stern-Weg 7, 8093, Zuerich, Switzerland.
Kretschmer K 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.
Rouse B Department of Pathobiology, College of Veterinary Medicine, University of Tennessee Knoxville, TN, 37996, USA.
Sparwasser T 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.

2014-12-16

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Immunity, inflammation and disease. - 2014

English 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.

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