Collagen-induced arthritis in the BB rat. Prevention of disease by treatment with CTLA-4-Ig
| Autor: | L J Mengle-Gaw, D B Knoerzer, B D Schwartz, R W Karr |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 1995 |
| Předmět: |
Cartilage
Articular Immunoconjugates T cell Lymphocyte Cooperation Molecular Sequence Data Type II collagen Receptors Antigen T-Cell Arthritis chemical and pharmacologic phenomena Major histocompatibility complex Autoimmune Diseases Abatacept Arthritis Rheumatoid Antigen CD28 Antigens Antigens CD medicine Animals CTLA-4 Antigen Genetic Predisposition to Disease Hypersensitivity Delayed Rats Inbred BB Autoantibodies biology Base Sequence T-cell receptor CD28 General Medicine medicine.disease Antigens Differentiation Rats Disease Models Animal medicine.anatomical_structure Immunology biology.protein B7-1 Antigen Cattle Collagen Disease Susceptibility Immunosuppressive Agents medicine.drug Research Article |
| Popis: | Antigen-specific T cell activation requires two independent signalling events, one mediated through T cell receptor engagement by the antigen-presenting cell-expressed peptide/class II major histocompatibility complex, and the second through the cognate interactions of costimulatory molecules expressed on the T cell and antigen-presenting cell. There is evidence from in vitro and in vivo experimental systems suggesting that the CD28/B7 costimulatory pathway is crucial for induction of maximal T cell proliferation and T helper-B cell collaboration for IgG production. This pathway can be blocked by CTLA-4-Ig, a soluble form of CTLA-4 which binds with high avidity to the CD28 ligands, B7-1 and B7-2. Here, we show that CTLA-4-Ig treatment prevents clinical and histological manifestations of disease in a collagen-induced arthritis model of rheumatoid arthritis in the diabetes resistant BB/Wor rat, when therapy is initiated before immunization with bovine type II collagen (BIIC). Anti-BIIC antibody titers are reduced in CTLA-4-Ig-treated rats compared to diseased control animals. Histologically, joints from CTLA-4-Ig-treated animals show no histological abnormalities, in contrast to control antibody-treated animals, which show complete erosion of the articular cartilage and bone. Despite the efficacy of CTLA-4-Ig in preventing clinical and histological signs of arthritis and reducing antibody responses to BIIC, delayed type hypersensitivity responses to collagen 18 d or more after CTLA-4-Ig treatment ends are similar in CTLA-4-Ig-treated and untreated rats, suggesting that the prolonged disease suppression observed does not result from induction of T cell anergy. |
| Databáze: | OpenAIRE |
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