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...
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | Clinical and Developmental Immunology |
| Online Access: | http://dx.doi.org/10.1155/2013/345092 |
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| author | Tove Eneljung Sara Tengvall Pernilla Jirholt Louise Henningsson Rikard Holmdahl Kenth Gustafsson Inger Gjertsson |
| author_facet | Tove Eneljung Sara Tengvall Pernilla Jirholt Louise Henningsson Rikard Holmdahl Kenth Gustafsson Inger Gjertsson |
| author_sort | Tove Eneljung |
| collection | DOAJ |
| 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 | Article |
| id | doaj-art-661f439371624f62a479be1b6729193f |
| institution | Kabale University |
| issn | 1740-2522 1740-2530 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
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| series | Clinical and Developmental Immunology |
| spelling | doaj-art-661f439371624f62a479be1b6729193f2025-02-03T01:22:12ZengWileyClinical and Developmental Immunology1740-25221740-25302013-01-01201310.1155/2013/345092345092Antigen-Specific Gene Therapy after Immunisation Reduces the Severity of Collagen-Induced ArthritisTove Eneljung0Sara Tengvall1Pernilla Jirholt2Louise Henningsson3Rikard Holmdahl4Kenth Gustafsson5Inger Gjertsson6Department of Rheumatology and Inflammatory Research, University of Gothenburg, P.O. Box 480, 405 30 Gothenburg, SwedenDepartment of Rheumatology and Inflammatory Research, University of Gothenburg, P.O. Box 480, 405 30 Gothenburg, SwedenDepartment of Rheumatology and Inflammatory Research, University of Gothenburg, P.O. Box 480, 405 30 Gothenburg, SwedenDepartment of Rheumatology and Inflammatory Research, University of Gothenburg, P.O. Box 480, 405 30 Gothenburg, SwedenMedical Inflammation Research, Karolinska Institute, 171 77 Stockholm, SwedenMolecular Immunology Unit, Institute of Child Health, UCL, 30 Guilford Street, London WC1N 1EH, UKDepartment of Rheumatology and Inflammatory Research, University of Gothenburg, P.O. Box 480, 405 30 Gothenburg, SwedenReestablishment 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.http://dx.doi.org/10.1155/2013/345092 |
| spellingShingle | Tove Eneljung Sara Tengvall Pernilla Jirholt Louise Henningsson Rikard Holmdahl Kenth Gustafsson Inger Gjertsson Antigen-Specific Gene Therapy after Immunisation Reduces the Severity of Collagen-Induced Arthritis Clinical and Developmental Immunology |
| 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 |
| url | http://dx.doi.org/10.1155/2013/345092 |
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