ANTI-CD3 therapy expands the numbers of CD4+ and CD8+ Treg cells and induces sustained amelioration of collagen-induced arthritis.
OBJECTIVE: To assess the therapeutic potential of anti-CD3 monoclonal antibodies (mAb) for rheumatoid arthritis, using collagen-induced arthritis as an animal model. METHODS: Arthritis was induced in DBA/1 mice by immunization with type II collagen. After disease onset, a single injection of anti-C...
Автори: | , , , |
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Формат: | Journal article |
Мова: | English |
Опубліковано: |
2010
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author | Notley, C McCann, F Inglis, J Williams, R |
author_facet | Notley, C McCann, F Inglis, J Williams, R |
author_sort | Notley, C |
collection | OXFORD |
description | OBJECTIVE: To assess the therapeutic potential of anti-CD3 monoclonal antibodies (mAb) for rheumatoid arthritis, using collagen-induced arthritis as an animal model. METHODS: Arthritis was induced in DBA/1 mice by immunization with type II collagen. After disease onset, a single injection of anti-CD3 mAb (20 microg/mouse) was administered, and arthritis severity was monitored over a 10-day period. RESULTS: Anti-CD3 mAb treatment resulted in a sustained reduction in disease activity, which was associated with an increase in the proportion of naturally occurring CD4+CD25+FoxP3+ regulatory T (Treg) cells and the generation of a population of CD8+CD25+FoxP3+ Treg cells. Anti-CD3 mAb treatment did not alter the capacity of CD4+ Treg cells to suppress effector T cell proliferation and interferon-gamma (IFNgamma) production in vitro. However, CD4+ Treg cells from both anti-CD3 mAb-treated and control mice were unable to suppress interleukin-17 (IL-17) production. In contrast, CD8+ Treg cells induced by anti-CD3 therapy suppressed IL-17 production as well as CD4+ T cell proliferation and IFNgamma production. CONCLUSION: These results show that anti-CD3 mAb treatment has important therapeutic potential for rheumatoid arthritis and has the capacity to generate antiarthritic CD8+ Treg cells and expand the relative numbers of CD4+ Treg cells. |
first_indexed | 2024-03-06T23:23:56Z |
format | Journal article |
id | oxford-uuid:69ba2ee8-353d-46d9-aa70-361cd4686532 |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-06T23:23:56Z |
publishDate | 2010 |
record_format | dspace |
spelling | oxford-uuid:69ba2ee8-353d-46d9-aa70-361cd46865322022-03-26T18:52:50ZANTI-CD3 therapy expands the numbers of CD4+ and CD8+ Treg cells and induces sustained amelioration of collagen-induced arthritis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:69ba2ee8-353d-46d9-aa70-361cd4686532EnglishSymplectic Elements at Oxford2010Notley, CMcCann, FInglis, JWilliams, R OBJECTIVE: To assess the therapeutic potential of anti-CD3 monoclonal antibodies (mAb) for rheumatoid arthritis, using collagen-induced arthritis as an animal model. METHODS: Arthritis was induced in DBA/1 mice by immunization with type II collagen. After disease onset, a single injection of anti-CD3 mAb (20 microg/mouse) was administered, and arthritis severity was monitored over a 10-day period. RESULTS: Anti-CD3 mAb treatment resulted in a sustained reduction in disease activity, which was associated with an increase in the proportion of naturally occurring CD4+CD25+FoxP3+ regulatory T (Treg) cells and the generation of a population of CD8+CD25+FoxP3+ Treg cells. Anti-CD3 mAb treatment did not alter the capacity of CD4+ Treg cells to suppress effector T cell proliferation and interferon-gamma (IFNgamma) production in vitro. However, CD4+ Treg cells from both anti-CD3 mAb-treated and control mice were unable to suppress interleukin-17 (IL-17) production. In contrast, CD8+ Treg cells induced by anti-CD3 therapy suppressed IL-17 production as well as CD4+ T cell proliferation and IFNgamma production. CONCLUSION: These results show that anti-CD3 mAb treatment has important therapeutic potential for rheumatoid arthritis and has the capacity to generate antiarthritic CD8+ Treg cells and expand the relative numbers of CD4+ Treg cells. |
spellingShingle | Notley, C McCann, F Inglis, J Williams, R ANTI-CD3 therapy expands the numbers of CD4+ and CD8+ Treg cells and induces sustained amelioration of collagen-induced arthritis. |
title | ANTI-CD3 therapy expands the numbers of CD4+ and CD8+ Treg cells and induces sustained amelioration of collagen-induced arthritis. |
title_full | ANTI-CD3 therapy expands the numbers of CD4+ and CD8+ Treg cells and induces sustained amelioration of collagen-induced arthritis. |
title_fullStr | ANTI-CD3 therapy expands the numbers of CD4+ and CD8+ Treg cells and induces sustained amelioration of collagen-induced arthritis. |
title_full_unstemmed | ANTI-CD3 therapy expands the numbers of CD4+ and CD8+ Treg cells and induces sustained amelioration of collagen-induced arthritis. |
title_short | ANTI-CD3 therapy expands the numbers of CD4+ and CD8+ Treg cells and induces sustained amelioration of collagen-induced arthritis. |
title_sort | anti cd3 therapy expands the numbers of cd4 and cd8 treg cells and induces sustained amelioration of collagen induced arthritis |
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