Collagen-induced arthritis in the BB rat. Prevention of disease by treatment with CTLA-4-Ig

J Clin Invest. 1995 Aug;96(2):987-93. doi: 10.1172/JCI118146.


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.

MeSH terms

  • Abatacept
  • Animals
  • Antigens, CD
  • Antigens, Differentiation / metabolism
  • Antigens, Differentiation / pharmacology
  • Antigens, Differentiation / therapeutic use*
  • Arthritis, Rheumatoid / chemically induced
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / pathology
  • Arthritis, Rheumatoid / prevention & control*
  • Autoantibodies / biosynthesis
  • Autoimmune Diseases / chemically induced
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / pathology
  • Autoimmune Diseases / prevention & control*
  • B7-1 Antigen / physiology*
  • Base Sequence
  • CD28 Antigens / physiology
  • CTLA-4 Antigen
  • Cartilage, Articular / pathology
  • Cattle
  • Collagen / toxicity*
  • Disease Models, Animal
  • Disease Susceptibility / immunology
  • Genetic Predisposition to Disease
  • Hypersensitivity, Delayed / etiology
  • Immunoconjugates / metabolism
  • Immunoconjugates / pharmacology
  • Immunoconjugates / therapeutic use*
  • Immunosuppressive Agents / metabolism
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use*
  • Lymphocyte Cooperation
  • Molecular Sequence Data
  • Rats
  • Rats, Inbred BB
  • Receptors, Antigen, T-Cell / immunology


  • Antigens, CD
  • Antigens, Differentiation
  • Autoantibodies
  • B7-1 Antigen
  • CD28 Antigens
  • CTLA-4 Antigen
  • Ctla4 protein, rat
  • Immunoconjugates
  • Immunosuppressive Agents
  • Receptors, Antigen, T-Cell
  • Abatacept
  • Collagen