title: Repeated Long-Term DT Application in the DEREG Mouse Induces a Neutralizing Anti-DT Antibody Response.
abstract: Regulatory T (Tregs) cells play an important role in mediating tolerance to self-antigens but can also mediate detrimental tolerance to tumours and pathogens in a Foxp3-dependent manner. Genetic tools exploiting thefoxp3locus including bacterial artificial chromosome- (BAC-) transgenic DEpletion of REGulatory T cells (DEREG) mice have provided essential information on Treg biology and the potential therapeutic modulation of tolerance. In DEREG mice, Foxp3+Tregs selectively express enhanced green fluorescent protein (eGFP) and diphtheria toxin (DT) receptor, allowing for the specific depletion of Tregs through DT administration. We here provide a detailed overview about an important consideration that long-term administration of DT induces a humoral immune response with an appropriate production of anti-DT antibodies that can inactivate DT and thus abrogate its effect in the DEREG mouse. Additionally, we showed that anti-DT mouse serum partially neutralized DT-induced Foxp3 inhibition.
authors.affiliation: Institute of Parasitology, University of Bern, Bern, Switzerland; Department of Infectious Diseases and Pathobiology, University of Bern, Bern, Switzerland.
authors.forename: Junhua
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Infectious Diseases and Pathobiology, University of Bern, Bern, Switzerland.
authors.forename: Myriam
authors.initials: M
authors.lastname: Siffert
authors.affiliation: Institute of Parasitology, University of Bern, Bern, Switzerland; Department of Infectious Diseases and Pathobiology, University of Bern, Bern, Switzerland.
authors.forename: Markus
authors.initials: M
authors.lastname: Spiliotis
authors.affiliation: Institute of Parasitology, University of Bern, Bern, Switzerland; Department of Infectious Diseases and Pathobiology, University of Bern, Bern, Switzerland.
authors.forename: Bruno
authors.identifier: 0000-0003-0782-3723
authors.initials: B
authors.lastname: Gottstein
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000096:biosynthesis / Q000276:immunology*; D001324:Autoantigens; D004167:Diphtheria Toxin / Q000008:administration & dosage* / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000235:genetics; D007108:Immune Tolerance; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D001324:Autoantigens; D004167:Diphtheria Toxin; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse