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Protection from experimental autoimmune encephalomyelitis by polyclonal IgG requires adjuvant-induced inflammation
BACKGROUND: Intravenous immunoglobulin (IVIG) proved to be an efficient anti-inflammatory treatment for a growing number of neuroinflammatory diseases and protects against the development of experimental autoimmune encephalomyelitis (EAE), a widely used animal model for multiple sclerosis (MS). METH...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4758141/ https://www.ncbi.nlm.nih.gov/pubmed/26893156 http://dx.doi.org/10.1186/s12974-016-0506-x |
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author | Quast, Isaak Keller, Christian W. Weber, Patrick Schneider, Christoph von Gunten, Stephan Lünemann, Jan D. |
author_facet | Quast, Isaak Keller, Christian W. Weber, Patrick Schneider, Christoph von Gunten, Stephan Lünemann, Jan D. |
author_sort | Quast, Isaak |
collection | PubMed |
description | BACKGROUND: Intravenous immunoglobulin (IVIG) proved to be an efficient anti-inflammatory treatment for a growing number of neuroinflammatory diseases and protects against the development of experimental autoimmune encephalomyelitis (EAE), a widely used animal model for multiple sclerosis (MS). METHODS: The clinical efficacy of IVIG and IVIG-derived F(ab’)(2) fragments, generated using the streptococcal cysteine proteinase Ide-S, was evaluated in EAE induced by active immunization and by adoptive transfer of myelin-specific T cells. Frequency, phenotype, and functional characteristics of T cell subsets and myeloid cells were determined by flow cytometry. Antibody binding to microbial antigen and cytokine production by innate immune cells was assessed by ELISA. RESULTS: We report that the protective effect of IVIG is lost in the adoptive transfer model of EAE and requires prophylactic administration during disease induction. IVIG-derived Fc fragments are not required for protection against EAE, since administration of F(ab’)(2) fragments fully recapitulated the clinical efficacy of IVIG. F(ab’)(2)-treated mice showed a substantial decrease in splenic effector T cell expansion and cytokine production (GM-CSF, IFN-γ, IL-17A) 9 days after immunization. Inhibition of effector T cell responses was not associated with an increase in total numbers of Tregs but with decreased activation of innate myeloid cells such as neutrophils, monocytes, and dendritic cells. Therapeutically effective IVIG-derived F(ab’)(2) fragments inhibited adjuvant-induced innate immune cell activation as determined by IL-12/23 p40 production and recognized mycobacterial antigens contained in Freund’s complete adjuvant which is required for induction of active EAE. CONCLUSIONS: Our data indicate that F(ab’)(2)-mediated neutralization of adjuvant contributes to the therapeutic efficacy of anti-inflammatory IgG. These findings might partly explain the discrepancy of IVIG efficacy in EAE and MS. |
format | Online Article Text |
id | pubmed-4758141 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-47581412016-02-19 Protection from experimental autoimmune encephalomyelitis by polyclonal IgG requires adjuvant-induced inflammation Quast, Isaak Keller, Christian W. Weber, Patrick Schneider, Christoph von Gunten, Stephan Lünemann, Jan D. J Neuroinflammation Research BACKGROUND: Intravenous immunoglobulin (IVIG) proved to be an efficient anti-inflammatory treatment for a growing number of neuroinflammatory diseases and protects against the development of experimental autoimmune encephalomyelitis (EAE), a widely used animal model for multiple sclerosis (MS). METHODS: The clinical efficacy of IVIG and IVIG-derived F(ab’)(2) fragments, generated using the streptococcal cysteine proteinase Ide-S, was evaluated in EAE induced by active immunization and by adoptive transfer of myelin-specific T cells. Frequency, phenotype, and functional characteristics of T cell subsets and myeloid cells were determined by flow cytometry. Antibody binding to microbial antigen and cytokine production by innate immune cells was assessed by ELISA. RESULTS: We report that the protective effect of IVIG is lost in the adoptive transfer model of EAE and requires prophylactic administration during disease induction. IVIG-derived Fc fragments are not required for protection against EAE, since administration of F(ab’)(2) fragments fully recapitulated the clinical efficacy of IVIG. F(ab’)(2)-treated mice showed a substantial decrease in splenic effector T cell expansion and cytokine production (GM-CSF, IFN-γ, IL-17A) 9 days after immunization. Inhibition of effector T cell responses was not associated with an increase in total numbers of Tregs but with decreased activation of innate myeloid cells such as neutrophils, monocytes, and dendritic cells. Therapeutically effective IVIG-derived F(ab’)(2) fragments inhibited adjuvant-induced innate immune cell activation as determined by IL-12/23 p40 production and recognized mycobacterial antigens contained in Freund’s complete adjuvant which is required for induction of active EAE. CONCLUSIONS: Our data indicate that F(ab’)(2)-mediated neutralization of adjuvant contributes to the therapeutic efficacy of anti-inflammatory IgG. These findings might partly explain the discrepancy of IVIG efficacy in EAE and MS. BioMed Central 2016-02-18 /pmc/articles/PMC4758141/ /pubmed/26893156 http://dx.doi.org/10.1186/s12974-016-0506-x Text en © Quast et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Quast, Isaak Keller, Christian W. Weber, Patrick Schneider, Christoph von Gunten, Stephan Lünemann, Jan D. Protection from experimental autoimmune encephalomyelitis by polyclonal IgG requires adjuvant-induced inflammation |
title | Protection from experimental autoimmune encephalomyelitis by polyclonal IgG requires adjuvant-induced inflammation |
title_full | Protection from experimental autoimmune encephalomyelitis by polyclonal IgG requires adjuvant-induced inflammation |
title_fullStr | Protection from experimental autoimmune encephalomyelitis by polyclonal IgG requires adjuvant-induced inflammation |
title_full_unstemmed | Protection from experimental autoimmune encephalomyelitis by polyclonal IgG requires adjuvant-induced inflammation |
title_short | Protection from experimental autoimmune encephalomyelitis by polyclonal IgG requires adjuvant-induced inflammation |
title_sort | protection from experimental autoimmune encephalomyelitis by polyclonal igg requires adjuvant-induced inflammation |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4758141/ https://www.ncbi.nlm.nih.gov/pubmed/26893156 http://dx.doi.org/10.1186/s12974-016-0506-x |
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