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Repetitive Pertussis Toxin Promotes Development of Regulatory T Cells and Prevents Central Nervous System Autoimmune Disease
Bacterial and viral infections have long been implicated in pathogenesis and progression of multiple sclerosis (MS). Incidence and severity of its animal model experimental autoimmune encephalomyelitis (EAE) can be enhanced by concomitant administration of pertussis toxin (PTx), the major virulence...
Autores principales: | , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2010
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3012729/ https://www.ncbi.nlm.nih.gov/pubmed/21209857 http://dx.doi.org/10.1371/journal.pone.0016009 |
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author | Weber, Martin S. Benkhoucha, Mahdia Lehmann-Horn, Klaus Hertzenberg, Deetje Sellner, Johann Santiago-Raber, Marie-Laure Chofflon, Michel Hemmer, Bernhard Zamvil, Scott S. Lalive, Patrice H. |
author_facet | Weber, Martin S. Benkhoucha, Mahdia Lehmann-Horn, Klaus Hertzenberg, Deetje Sellner, Johann Santiago-Raber, Marie-Laure Chofflon, Michel Hemmer, Bernhard Zamvil, Scott S. Lalive, Patrice H. |
author_sort | Weber, Martin S. |
collection | PubMed |
description | Bacterial and viral infections have long been implicated in pathogenesis and progression of multiple sclerosis (MS). Incidence and severity of its animal model experimental autoimmune encephalomyelitis (EAE) can be enhanced by concomitant administration of pertussis toxin (PTx), the major virulence factor of Bordetella pertussis. Its adjuvant effect at the time of immunization with myelin antigen is attributed to an unspecific activation and facilitated migration of immune cells across the blood brain barrier into the central nervous system (CNS). In order to evaluate whether recurring exposure to bacterial antigen may have a differential effect on development of CNS autoimmunity, we repetitively administered PTx prior to immunization. Mice weekly injected with PTx were largely protected from subsequent EAE induction which was reflected by a decreased proliferation and pro-inflammatory differentiation of myelin-reactive T cells. Splenocytes isolated from EAE-resistant mice predominantly produced IL-10 upon re-stimulation with PTx, while non-specific immune responses were unchanged. Longitudinal analyses revealed that repetitive exposure of mice to PTx gradually elevated serum levels for TGF-β and IL-10 which was associated with an expansion of peripheral CD4(+)CD25(+)FoxP3(+) regulatory T cells (Treg). Increased frequency of Treg persisted upon immunization and thereafter. Collectively, these data suggest a scenario in which repetitive PTx treatment protects mice from development of CNS autoimmune disease through upregulation of regulatory cytokines and expansion of CD4(+)CD25(+)FoxP3(+) Treg. Besides its therapeutic implication, this finding suggests that encounter of the immune system with microbial products may not only be part of CNS autoimmune disease pathogenesis but also of its regulation. |
format | Text |
id | pubmed-3012729 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-30127292011-01-05 Repetitive Pertussis Toxin Promotes Development of Regulatory T Cells and Prevents Central Nervous System Autoimmune Disease Weber, Martin S. Benkhoucha, Mahdia Lehmann-Horn, Klaus Hertzenberg, Deetje Sellner, Johann Santiago-Raber, Marie-Laure Chofflon, Michel Hemmer, Bernhard Zamvil, Scott S. Lalive, Patrice H. PLoS One Research Article Bacterial and viral infections have long been implicated in pathogenesis and progression of multiple sclerosis (MS). Incidence and severity of its animal model experimental autoimmune encephalomyelitis (EAE) can be enhanced by concomitant administration of pertussis toxin (PTx), the major virulence factor of Bordetella pertussis. Its adjuvant effect at the time of immunization with myelin antigen is attributed to an unspecific activation and facilitated migration of immune cells across the blood brain barrier into the central nervous system (CNS). In order to evaluate whether recurring exposure to bacterial antigen may have a differential effect on development of CNS autoimmunity, we repetitively administered PTx prior to immunization. Mice weekly injected with PTx were largely protected from subsequent EAE induction which was reflected by a decreased proliferation and pro-inflammatory differentiation of myelin-reactive T cells. Splenocytes isolated from EAE-resistant mice predominantly produced IL-10 upon re-stimulation with PTx, while non-specific immune responses were unchanged. Longitudinal analyses revealed that repetitive exposure of mice to PTx gradually elevated serum levels for TGF-β and IL-10 which was associated with an expansion of peripheral CD4(+)CD25(+)FoxP3(+) regulatory T cells (Treg). Increased frequency of Treg persisted upon immunization and thereafter. Collectively, these data suggest a scenario in which repetitive PTx treatment protects mice from development of CNS autoimmune disease through upregulation of regulatory cytokines and expansion of CD4(+)CD25(+)FoxP3(+) Treg. Besides its therapeutic implication, this finding suggests that encounter of the immune system with microbial products may not only be part of CNS autoimmune disease pathogenesis but also of its regulation. Public Library of Science 2010-12-30 /pmc/articles/PMC3012729/ /pubmed/21209857 http://dx.doi.org/10.1371/journal.pone.0016009 Text en Weber et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Weber, Martin S. Benkhoucha, Mahdia Lehmann-Horn, Klaus Hertzenberg, Deetje Sellner, Johann Santiago-Raber, Marie-Laure Chofflon, Michel Hemmer, Bernhard Zamvil, Scott S. Lalive, Patrice H. Repetitive Pertussis Toxin Promotes Development of Regulatory T Cells and Prevents Central Nervous System Autoimmune Disease |
title | Repetitive Pertussis Toxin Promotes Development of Regulatory T Cells and Prevents Central Nervous System Autoimmune Disease |
title_full | Repetitive Pertussis Toxin Promotes Development of Regulatory T Cells and Prevents Central Nervous System Autoimmune Disease |
title_fullStr | Repetitive Pertussis Toxin Promotes Development of Regulatory T Cells and Prevents Central Nervous System Autoimmune Disease |
title_full_unstemmed | Repetitive Pertussis Toxin Promotes Development of Regulatory T Cells and Prevents Central Nervous System Autoimmune Disease |
title_short | Repetitive Pertussis Toxin Promotes Development of Regulatory T Cells and Prevents Central Nervous System Autoimmune Disease |
title_sort | repetitive pertussis toxin promotes development of regulatory t cells and prevents central nervous system autoimmune disease |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3012729/ https://www.ncbi.nlm.nih.gov/pubmed/21209857 http://dx.doi.org/10.1371/journal.pone.0016009 |
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