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Tolerance induction with T cell-dependent protein antigens induces regulatory sialylated IgGs

Oefner, Carolin M.; Winkler, Andre; Hess, Constanze; Lorenz, Alexandra K.; Holecska, Vivien; Huxdorf, Melanie; Schommartz, Tim; Petzold, Dominique; Bitterling, Josephine and Schoen, Anna-Lena, et al. (2012) In Journal of Allergy and Clinical Immunology 129(6). p.1647-1647
Abstract
Background: Under inflammatory conditions, T cell-dependent (TD) protein antigens induce proinflammatory T-and B-cell responses. In contrast, tolerance induction by TD antigens without costimulation triggers the development of regulatory T cells. Under both conditions, IgG antibodies are generated, but whether they have different immunoregulatory functions remains elusive. Objective: It was shown recently that proinflammatory or anti-inflammatory effector functions of IgG molecules are determined by different Fc N-linked glycosylation patterns. We sought to examine the Fc glycosylation and anti-inflammatory quality of IgG molecules formed on TD tolerance induction. Methods: We administered chicken ovalbumin (OVA) with or without costimulus... (More)
Background: Under inflammatory conditions, T cell-dependent (TD) protein antigens induce proinflammatory T-and B-cell responses. In contrast, tolerance induction by TD antigens without costimulation triggers the development of regulatory T cells. Under both conditions, IgG antibodies are generated, but whether they have different immunoregulatory functions remains elusive. Objective: It was shown recently that proinflammatory or anti-inflammatory effector functions of IgG molecules are determined by different Fc N-linked glycosylation patterns. We sought to examine the Fc glycosylation and anti-inflammatory quality of IgG molecules formed on TD tolerance induction. Methods: We administered chicken ovalbumin (OVA) with or without costimulus to mice and analyzed OVA-reactive IgG Fc glycosylation. The anti-inflammatory function of differentially glycosylated anti-OVA IgGs was further investigated in studies with dendritic cell cultures and in an in vivo model of allergic airway disease. Additionally, we analyzed the Fc glycosylation pattern of birch pollen-reactive serum IgGs after successful allergen-specific immunotherapy in patients. Results: Stimulation with TD antigens under inflammatory conditions induces plasma cells expressing low levels of alpha 2,6-sialyltransferase and producing desialylated IgGs. In contrast, plasma cells induced on tolerance induction did not downregulate alpha 2,6-sialyltransferase expression and secreted immunosuppressive sialylated IgGs that were sufficient to block antigen-specific T- and B-cell responses, dendritic cell maturation, and allergic airway inflammation. Importantly, successful specific immunotherapy in allergic patients also induced sialylated allergen-specific IgGs. Conclusions: Our data show a novel antigen-specific immunoregulatory mechanism mediated by anti-inflammatory sialylated IgGs that are formed on TD tolerance induction. These findings might help to develop novel antigen-specific therapies for the treatment of allergy and autoimmunity. (J Allergy Clin Immunol 2012;129:1647-55.) (Less)
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keywords
Tolerance, IgG antibodies, IgG sialylation, dendritic cells, allergy, asthma, antigen-specific immunotherapy, antigen-specific tolerance, antibody therapy
in
Journal of Allergy and Clinical Immunology
volume
129
issue
6
pages
1647 - 1647
publisher
Elsevier
external identifiers
  • wos:000304764600027
  • scopus:84861691610
ISSN
1097-6825
DOI
10.1016/j.jaci.2012.02.037
language
English
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yes
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94a9ed75-2285-4b8a-bfe2-704cd8bf3d0f (old id 2896877)
date added to LUP
2012-08-01 09:44:29
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2017-10-29 03:48:15
@article{94a9ed75-2285-4b8a-bfe2-704cd8bf3d0f,
  abstract     = {Background: Under inflammatory conditions, T cell-dependent (TD) protein antigens induce proinflammatory T-and B-cell responses. In contrast, tolerance induction by TD antigens without costimulation triggers the development of regulatory T cells. Under both conditions, IgG antibodies are generated, but whether they have different immunoregulatory functions remains elusive. Objective: It was shown recently that proinflammatory or anti-inflammatory effector functions of IgG molecules are determined by different Fc N-linked glycosylation patterns. We sought to examine the Fc glycosylation and anti-inflammatory quality of IgG molecules formed on TD tolerance induction. Methods: We administered chicken ovalbumin (OVA) with or without costimulus to mice and analyzed OVA-reactive IgG Fc glycosylation. The anti-inflammatory function of differentially glycosylated anti-OVA IgGs was further investigated in studies with dendritic cell cultures and in an in vivo model of allergic airway disease. Additionally, we analyzed the Fc glycosylation pattern of birch pollen-reactive serum IgGs after successful allergen-specific immunotherapy in patients. Results: Stimulation with TD antigens under inflammatory conditions induces plasma cells expressing low levels of alpha 2,6-sialyltransferase and producing desialylated IgGs. In contrast, plasma cells induced on tolerance induction did not downregulate alpha 2,6-sialyltransferase expression and secreted immunosuppressive sialylated IgGs that were sufficient to block antigen-specific T- and B-cell responses, dendritic cell maturation, and allergic airway inflammation. Importantly, successful specific immunotherapy in allergic patients also induced sialylated allergen-specific IgGs. Conclusions: Our data show a novel antigen-specific immunoregulatory mechanism mediated by anti-inflammatory sialylated IgGs that are formed on TD tolerance induction. These findings might help to develop novel antigen-specific therapies for the treatment of allergy and autoimmunity. (J Allergy Clin Immunol 2012;129:1647-55.)},
  author       = {Oefner, Carolin M. and Winkler, Andre and Hess, Constanze and Lorenz, Alexandra K. and Holecska, Vivien and Huxdorf, Melanie and Schommartz, Tim and Petzold, Dominique and Bitterling, Josephine and Schoen, Anna-Lena and Stoehr, Alexander D. and Van, Dana Vu and Darcan-Nikolaisen, Yasemin and Blanchard, Veronique and Schmudde, Inken and Laumonnier, Yves and Stroever, Heike A. and Hegazy, Ahmed N. and Eiglmeier, Susanne and Schoen, Carolin T. and Mertes, Maria M. M. and Loddenkemper, Christoph and Loehning, Max and Koenig, Peter and Petersen, Arnd and Luger, Elke O. and Collin, Mattias and Koehl, Joerg and Hutloff, Andreas and Hamelmann, Eckard and Berger, Markus and Wardemann, Hedda and Ehlers, Marc},
  issn         = {1097-6825},
  keyword      = {Tolerance,IgG antibodies,IgG sialylation,dendritic cells,allergy,asthma,antigen-specific immunotherapy,antigen-specific tolerance,antibody therapy},
  language     = {eng},
  number       = {6},
  pages        = {1647--1647},
  publisher    = {Elsevier},
  series       = {Journal of Allergy and Clinical Immunology},
  title        = {Tolerance induction with T cell-dependent protein antigens induces regulatory sialylated IgGs},
  url          = {http://dx.doi.org/10.1016/j.jaci.2012.02.037},
  volume       = {129},
  year         = {2012},
}