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- Title
Engagement of the CD137 (4-1BB) costimulatory molecule inhibits and reverses the autoimmune process in collagen-induced arthritis and establishes lasting disease resistance.
- Authors
Foell, Juergen L.; Diez-Mendiondo, Belkis I.; Diez, Oliver H.; Holzer, Ursula; Ruck, Peter; Bapat, Abhijit S.; Hoffmann, Michael K.; Mittler, Robert S.; Dannecker, Guenther E.
- Abstract
Agonistic antibodies against CD137 act as costimulators in the activation of CD8 T cells. They enhance the immune response against syngeneic tumour grafts and suppress T cell-dependent humoral immune responses in vivo. The present study was undertaken to determine whether suppression of antibody production by anti-CD137 mAb affects the development of collagen-induced arthritis (CIA). Male DBA/1J mice were immunized with bovine collagen II (CII) and treated with an agonistic anti-CD137 mAb or an isotype-matched control mAb. Mice were assessed regularly for macro- and microscopic signs of arthritis and for the appearance of collagen-specific antibody production. Interferon (IFN)-γ determination, FACS analysis of splenocytes and histopathological joint examinations were performed after the animals were killed. Administration of anti-CD137 mAb at the time of collagen immunization blocked the development of disease and inhibited the humoral immune response against CII. Agonistic anti-CD137 mAb exhibited therapeutic efficacy even after the immune response to CII had succeeded and the disease became apparent. Furthermore, it induced a protective memory in the animals, enabling resistance to subsequent challenges with the pathogenic antigen. Our results suggest a key role for CD137 in the pathogenesis of CIA. This model provides insights into immunoregulatory conditions that control the pathogenesis of autoimmune diseases.
- Subjects
T cells; CELL receptors; BINDING sites; LABORATORY mice; IMMUNOLOGIC diseases; AUTOIMMUNE diseases
- Publication
Immunology, 2004, Vol 113, Issue 1, p89
- ISSN
0019-2805
- Publication type
Article
- DOI
10.1111/j.1365-2567.2004.01952.x