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Antigen-Specific Gene Therapy after Immunisation Reduces the Severity of Collagen-Induced Arthritis
Reestablishment of tolerance induction in rheumatoid arthritis (RA) would be an optimal treatment with few, if any, side effects. However, to develop such a treatment further insights in the immunological mechanisms governing tolerance are needed. We have developed a model of antigen-specific tolera...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858880/ https://www.ncbi.nlm.nih.gov/pubmed/24371448 http://dx.doi.org/10.1155/2013/345092 |
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author | Eneljung, Tove Tengvall, Sara Jirholt, Pernilla Henningsson, Louise Holmdahl, Rikard Gustafsson, Kenth Gjertsson, Inger |
author_facet | Eneljung, Tove Tengvall, Sara Jirholt, Pernilla Henningsson, Louise Holmdahl, Rikard Gustafsson, Kenth Gjertsson, Inger |
author_sort | Eneljung, Tove |
collection | PubMed |
description | Reestablishment of tolerance induction in rheumatoid arthritis (RA) would be an optimal treatment with few, if any, side effects. However, to develop such a treatment further insights in the immunological mechanisms governing tolerance are needed. We have developed a model of antigen-specific tolerance in collagen type II (CII) induced arthritis (CIA) using lentivirus-based gene therapy. The immunodominant epitope of CII was inserted into a lentivirus vector to achieve expression on the MHC class II molecule and the lentiviral particles were subsequently intravenously injected at different time points during CIA. Injection of lentiviral particles in early phases of CIA, that is, at day 7 or day 26 after CII immunisation, partially prevented development of arthritis, decreased the serum levels of CII-specific IgG antibodies, and enhanced the suppressive function of CII-specific T regulatory cells. When lentiviral particles were injected during manifest arthritis, that is, at day 31 after CII immunisation, the severity of arthritis progression was ameliorated, the levels of CII-specific IgG antibodies decreased and the proportion of T regulatory cells increased. Thus, antigen-specific gene therapy is effective when administered throughout the inflammatory course of arthritis and offers a good model for investigation of the basic mechanisms during tolerance in CIA. |
format | Online Article Text |
id | pubmed-3858880 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-38588802013-12-26 Antigen-Specific Gene Therapy after Immunisation Reduces the Severity of Collagen-Induced Arthritis Eneljung, Tove Tengvall, Sara Jirholt, Pernilla Henningsson, Louise Holmdahl, Rikard Gustafsson, Kenth Gjertsson, Inger Clin Dev Immunol Research Article Reestablishment of tolerance induction in rheumatoid arthritis (RA) would be an optimal treatment with few, if any, side effects. However, to develop such a treatment further insights in the immunological mechanisms governing tolerance are needed. We have developed a model of antigen-specific tolerance in collagen type II (CII) induced arthritis (CIA) using lentivirus-based gene therapy. The immunodominant epitope of CII was inserted into a lentivirus vector to achieve expression on the MHC class II molecule and the lentiviral particles were subsequently intravenously injected at different time points during CIA. Injection of lentiviral particles in early phases of CIA, that is, at day 7 or day 26 after CII immunisation, partially prevented development of arthritis, decreased the serum levels of CII-specific IgG antibodies, and enhanced the suppressive function of CII-specific T regulatory cells. When lentiviral particles were injected during manifest arthritis, that is, at day 31 after CII immunisation, the severity of arthritis progression was ameliorated, the levels of CII-specific IgG antibodies decreased and the proportion of T regulatory cells increased. Thus, antigen-specific gene therapy is effective when administered throughout the inflammatory course of arthritis and offers a good model for investigation of the basic mechanisms during tolerance in CIA. Hindawi Publishing Corporation 2013 2013-11-26 /pmc/articles/PMC3858880/ /pubmed/24371448 http://dx.doi.org/10.1155/2013/345092 Text en Copyright © 2013 Tove Eneljung et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Eneljung, Tove Tengvall, Sara Jirholt, Pernilla Henningsson, Louise Holmdahl, Rikard Gustafsson, Kenth Gjertsson, Inger Antigen-Specific Gene Therapy after Immunisation Reduces the Severity of Collagen-Induced Arthritis |
title | Antigen-Specific Gene Therapy after Immunisation Reduces the Severity of Collagen-Induced Arthritis |
title_full | Antigen-Specific Gene Therapy after Immunisation Reduces the Severity of Collagen-Induced Arthritis |
title_fullStr | Antigen-Specific Gene Therapy after Immunisation Reduces the Severity of Collagen-Induced Arthritis |
title_full_unstemmed | Antigen-Specific Gene Therapy after Immunisation Reduces the Severity of Collagen-Induced Arthritis |
title_short | Antigen-Specific Gene Therapy after Immunisation Reduces the Severity of Collagen-Induced Arthritis |
title_sort | antigen-specific gene therapy after immunisation reduces the severity of collagen-induced arthritis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858880/ https://www.ncbi.nlm.nih.gov/pubmed/24371448 http://dx.doi.org/10.1155/2013/345092 |
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