Advantages of Foxp3+ regulatory T cell depletion using DEREG mice

Immunity, Inflammation and Disease

Christian T. Mayer¹  Katharina Lahl⁸  Pedro Milanez-Almeida⁵  Deepika Watts³  Ulf Dittmer²  Nanna Fyhrquist⁷  Jochen Huehn⁵  Manfred Kopf⁶  Karsten Kretschmer³  Barry Rouse⁴ 

[1] 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, Hannover, Germany;Institute for Virology, University Hospital Essen, University Duisburg-Essen, Essen, Germany;Molecular and Cellular Immunology/Immune Regulation, DFG-Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, Germany;Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, USA;Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany;Institute for Molecular Health Sciences, Swiss Federal Institute of Technology Zuerich, Zuerich, Switzerland;Unit of Systems Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland;Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA

关键词: Autoimmunity;    DEREG;    diphtheria toxin (DT);    regulatory T cells;    tolerance;    Treg;   

DOI  :  10.1002/iid3.33

来源: Wiley

【 摘 要 】

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.

【 授权许可】

CC BY-NC-ND   
© 2014 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd.

Creative Commons Attribution-NonCommercial-NoDerivsLicense, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.