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...

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Автори: Notley, C, McCann, F, Inglis, J, Williams, R
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.
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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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