Therapy against murine collagen-induced arthritis with T cell receptor V beta-specific antibodies.
Immunization with native type II collagen (CII) of susceptible strains of mice (H-2q) induces a rheumatoid arthritis-like disease. Collagen-induced arthritis (CIA) is an experimental model for T cell-mediated autoimmune disease. To investigate the T cell receptor (TcR) repertoire involved in the pathogenesis of CIA, CII-primed DBA/1 mice were treated with various TcR V beta-specific monoclonal antibodies (mAb) using a protocol resulting in a long-term elimination of the target T cells. In vivo treatment with anti-CD4 mAb led to nearly complete protection against CIA. Mice injected with anti-V beta 8.1, 2 or anti-V beta 5.1, 2 mAb had a reduced incidence of arthritis (respectively 28.6% and 50% vs 84.6% for the control group). Administration of anti-V beta 2 mAb delayed the onset of the disease whereas injection of anti-V beta 6 or anti-V beta 11 mAb did not alter CIA. Moreover, the combined treatment with anti-V beta 2 and anti-V beta 5 mAb efficiently reduced the development of CIA. The humoral response to CII was down-regulated only in the groups of mice that were improved by the treatment. In vitro proliferative response to CII of lymph node cells from primed DBA/1 was partially blocked by addition of several anti-V beta mAb. Thus, our findings suggest that the overall T cell response to CII may be polyclonal while the T cell clones involved in the pathogenesis of CIA express a limited number of V beta chains.
Chiocchia
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INSERM U.283, Hôpital Cochin, Paris, France.
Boissier
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MC
Fournier
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000917:Antibody Formation; D001172:Arthritis, Rheumatoid / Q000628:therapy*; D003094:Collagen / Q000276:immunology*; D007518:Isoantibodies / Q000627:therapeutic use*; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007518:Isoantibodies; D016693:Receptors, Antigen, T-Cell, alpha-beta; D003094:Collagen