Repeated Long-Term DT Application in the DEREG Mouse Induces a Neutralizing Anti-DT Antibody Response

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 the foxp3 locus including bacterial artificial chromosome- (BAC-) transgenic DEpletion o...

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Main Authors: Junhua Wang, Myriam Siffert, Markus Spiliotis, Bruno Gottstein
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2016/1450398
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author Junhua Wang
Myriam Siffert
Markus Spiliotis
Bruno Gottstein
author_facet Junhua Wang
Myriam Siffert
Markus Spiliotis
Bruno Gottstein
author_sort Junhua Wang
collection DOAJ
description 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 the foxp3 locus 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.
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spelling doaj-art-94f46cdbcdbc47feafae8da7a91228d02025-02-03T01:01:11ZengWileyJournal of Immunology Research2314-88612314-71562016-01-01201610.1155/2016/14503981450398Repeated Long-Term DT Application in the DEREG Mouse Induces a Neutralizing Anti-DT Antibody ResponseJunhua Wang0Myriam Siffert1Markus Spiliotis2Bruno Gottstein3Institute of Parasitology, University of Bern, Bern, SwitzerlandDepartment of Infectious Diseases and Pathobiology, University of Bern, Bern, SwitzerlandInstitute of Parasitology, University of Bern, Bern, SwitzerlandInstitute of Parasitology, University of Bern, Bern, SwitzerlandRegulatory 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 the foxp3 locus 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.http://dx.doi.org/10.1155/2016/1450398
spellingShingle Junhua Wang
Myriam Siffert
Markus Spiliotis
Bruno Gottstein
Repeated Long-Term DT Application in the DEREG Mouse Induces a Neutralizing Anti-DT Antibody Response
Journal of Immunology Research
title Repeated Long-Term DT Application in the DEREG Mouse Induces a Neutralizing Anti-DT Antibody Response
title_full Repeated Long-Term DT Application in the DEREG Mouse Induces a Neutralizing Anti-DT Antibody Response
title_fullStr Repeated Long-Term DT Application in the DEREG Mouse Induces a Neutralizing Anti-DT Antibody Response
title_full_unstemmed Repeated Long-Term DT Application in the DEREG Mouse Induces a Neutralizing Anti-DT Antibody Response
title_short Repeated Long-Term DT Application in the DEREG Mouse Induces a Neutralizing Anti-DT Antibody Response
title_sort repeated long term dt application in the dereg mouse induces a neutralizing anti dt antibody response
url http://dx.doi.org/10.1155/2016/1450398
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AT myriamsiffert repeatedlongtermdtapplicationinthederegmouseinducesaneutralizingantidtantibodyresponse
AT markusspiliotis repeatedlongtermdtapplicationinthederegmouseinducesaneutralizingantidtantibodyresponse
AT brunogottstein repeatedlongtermdtapplicationinthederegmouseinducesaneutralizingantidtantibodyresponse