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-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.