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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.

Original publication

DOI

10.1002/art.25058

Type

Journal article

Journal

Arthritis and rheumatism

Publication Date

01/2010

Volume

62

Pages

171 - 178

Addresses

Imperial College London, London, UK.

Keywords

Joints, Lymph Nodes, CD8-Positive T-Lymphocytes, Cells, Cultured, Hindlimb, Animals, Mice, Inbred DBA, Mice, Arthritis, Experimental, Antirheumatic Agents, Antigens, CD3, Interleukin-17, Antibodies, Monoclonal, Cell Count, Cell Proliferation, Male, T-Lymphocytes, Regulatory, Interferon-gamma