Ms Morgan and Dr. Sutmuller contributed equally to this work.
CD25+ cell depletion hastens the onset of severe disease in collagen-induced arthritis
Version of Record online: 6 MAY 2003
Copyright © 2003 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 48, Issue 5, pages 1452–1460, May 2003
How to Cite
Morgan, M. E., Sutmuller, R. P. M., Witteveen, H. J., van Duivenvoorde, L. M., Zanelli, E., Melief, C. J. M., Snijders, A., Offringa, R., de Vries, R. R. P. and Toes, R. E. M. (2003), CD25+ cell depletion hastens the onset of severe disease in collagen-induced arthritis. Arthritis & Rheumatism, 48: 1452–1460. doi: 10.1002/art.11063
- Issue online: 6 MAY 2003
- Version of Record online: 6 MAY 2003
- Manuscript Accepted: 6 FEB 2003
- Manuscript Received: 7 AUG 2002
- Netherlands Organization for Scientific Research (project). Grant Numbers: 901-09-262, 940-35-035
- Dutch Arthritis Foundation
- Gisela Thier Fonds
- Dutch Royal Academy of Arts and Sciences
CD4+,CD25+ T regulatory cells may offer opportunities to intervene in the course of autoimmune disease. We wished to evaluate their potential for influencing systemic and chronic joint inflammation by investigating their involvement in collagen-induced arthritis (CIA).
We depleted DBA/1 mice of CD25+ regulatory cells by injection of a depleting monoclonal antibody specific for CD25 14 days before a single immunization with type II collagen (CII) in Freund's complete adjuvant. CD4+,CD25+ T cells were adoptively transferred to some groups of mice during immunization. Mice were then scored for signs of arthritis, and blood was taken periodically to measure the amounts of CII-specific antibodies. Splenocytes of treated mice were examined in vitro to determine the effects of depletion on proliferation to CII and control antigens.
CD25+ cell–depleted DBA/1 mice had significantly more severe disease than control mice following collagen immunization. The magnified severity was also accompanied by higher antibody titers against collagen, and in vitro tests showed increased proliferation of collagen-specific T cells. Adoptively transferring CD4+,CD25+ T cells into depleted mice was shown to reverse the heightened severity. Control mice, which were depleted and immunized with the neoantigen keyhole limpet hemocyanin (KLH), had neither an increased antibody response toward KLH nor an augmented proliferative response, indicating that CD25+ cell depletion preferentially affects immunity against self antigen.
These results establish a link between CD4+,CD25+ regulatory cells and CIA and provide a rationale for investigating CD4+,CD25+ T regulatory cells in the treatment and prevention of arthritis.