CD137 costimulatory T cell receptor engagement reverses acute disease in lupus-prone NZB × NZW F1 mice
AUTOR(ES)
Foell, Juergen
FONTE
American Society for Clinical Investigation
RESUMO
Systemic lupus erythematosus (SLE) is a CD4+ T cell–dependent, immune complex–mediated, autoimmune disease that primarily affects women of childbearing age. Generation of high-titer affinity-matured IgG autoantibodies, specific for double-stranded DNA and other nuclear antigens, coincides with disease progression. Current forms of treatment of SLE including glucocorticosteroids are often inadequate and induce severe side effects. Immunological approaches for treating SLE in mice using anti-CD4 mAb’s or CTLA4-Ig and anti-CD154 mAb’s have proven to be effective. However, like steroid treatment, these regimens induce global immunosuppression, and their withdrawal allows for disease progression. In this report we show that lupus-prone NZB × NZW F1 mice given three injections of anti-CD137 (4-1BB) mAb’s between 26 and 35 weeks of age reversed acute disease, blocked chronic disease, and extended the mice’s lifespan from 10 months to more than 2 years. Autoantibody production in recipients was rapidly suppressed without inducing immunosuppression. Successful treatment could be traced to the fact that NZB × NZW F1 mice, regardless of their age or disease status, could not maintain pathogenic IgG autoantibody production in the absence of continuous CD4+ T cell help. Our data support the hypothesis that CD137-mediated signaling anergized CD4+ T cells during priming at the DC interface.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=155050Documentos Relacionados
- Interleukin 6 promotes murine lupus in NZB/NZW F1 mice.
- Influence of dietary restriction on immunologic function and renal disease in (NZB × NZW) F1 mice
- Polyclonal B cell activation in lupus-prone mice precedes and predicts the development of autoimmune disease.
- Genetic analysis of the NZB contribution to lupus-like autoimmune disease in (NZB x NZW)F1 mice.
- Effects on prolactin secretion and binding to dopaminergic receptors in sleep-deprived lupus-prone mice