1. Interference with CD28, CD80, CD86 or CD152 in collagen-induced arthritis. Limited role of IFN-gamma in anti-B7-mediated suppression of disease.
- Author
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Tellander AC, Pettersson U, Runström A, Andersson M, and Michaëlsson E
- Subjects
- Abatacept, Animals, Antibodies, Blocking pharmacology, Antibodies, Monoclonal administration & dosage, B7-2 Antigen, CD28 Antigens metabolism, CTLA-4 Antigen, Immunoglobulin G blood, Injections, Intraperitoneal, Lymphocyte Activation immunology, Male, Membrane Glycoproteins antagonists & inhibitors, Mice, Mice, Inbred BALB C, Mice, Inbred DBA, Signal Transduction immunology, T-Lymphocytes immunology, Antibodies, Monoclonal pharmacology, Antigens, CD immunology, Antigens, Differentiation immunology, Arthritis, Experimental immunology, B7-1 Antigen immunology, CD28 Antigens immunology, Collagen immunology, Immune Tolerance physiology, Immunoconjugates, Interferon-gamma physiology, Membrane Glycoproteins immunology
- Abstract
We have investigated interference with co-stimulation by administering mAbs towards CD28, CD80, CD86, and CD152 in mice immunized for the development of collagen-induced arthritis (CIA). Anti-CD80 and anti-CD86 treatment inhibited disease score and incidence, whereas anti-CD28 treatment led only to a delayed disease onset. Administration of anti-CD152 had no effect. The CII-specific Ab-response was suppressed by the co-stimulatory blockade, with a stronger effect on IgG1 than on IgG2a. The CII-driven T cell proliferation, on the other hand, was not affected. Furthermore, T cells primed in the presence of either anti-B7 or anti-CD28 produced markedly increased amounts of IFN-gamma in response to CII. To investigate whether this increase in IFN-gamma was related to disease suppression, IFN-gamma-deficient mice were immunized with CII, treated with anti-B7 and followed for the development of arthritis. As in the wild-type mice, administration of anti-B7 to IFN-gamma-deficient mice led to a reduced disease incidence and severity as well as reduced anti-CII IgG titers. Collectively, these data stress the importance of co-stimulation for the delivery of B cell help rather than for production of Th1 cytokines. We also demonstrate that the enhanced production of IFN-gamma observed after B7-blockade is not accountable for the anti-B7 mediated inhibition of CIA., (Copyright 2001 Academic Press.)
- Published
- 2001
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