Therapy against murine collagen‐induced arthritis with T cell receptor Vβ‐specific antibodies

Abstract

Immunization with native type II collagen (CII) of susceptible strains of mice (H‐2^q) 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_bT‐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_β8.1,2 or anti‐V_β5.1,2 mAb had a reduced incidence of arthritis (respectively 28.6% and 50% vs 84.6% for the control group). Administration of anti‐V_bT2 mAb delayed the onset of the disease whereas injection of anti‐V_bT6 or anti‐V_bT11 mAb did not alter CIA. Moreover, the combined treatment with anti‐V_bT2 and anti‐V_β5 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_bT 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_β chains.