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‐CD3 mAb (20 μg/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‐γ (IFNγ) 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 IFNγ 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.