T-CELL-TARGETED IMMUNOTHERAPY IN MURINE COLLAGEN-INDUCED ARTHRITIS

Counteracting the effect of autoimmunity can be achieved by elimination or inactivation of autoreactive T cells. We have focused on two approaches targeting on autoaggressive T cells in the model of collagen-induced arthritis (CIA) in mice. First, type II collagen (CII) primed DBA /1 mice were treated with various monoclonal antibodies (mAb) specific for the beta chains of the T cell receptor (TCR) using a protocol resulting in a long-term elimination of the target T cells. Indeed, CIA could be suppressed by injection of anti-Vbeta8.1,2 mA b and down-regulated by that of anti-Vbeta2 and/or anti-Vbeta5, presumably by deleting pathogenic T cell clones. In contrast, treatment with either antiVbeta6 or anti-Vbeta11 mAb did not alter CIA. Second, we generated CII-specific T cell hybrid clones that recognize the antigenic peptides in association with K(q) and IA(q) molecules respectively for CD8+ and CD4+ cells. Vaccination with the irradiated hybrid clones, 3 weeks prior to immunization, was effective in preventing the development of arthritis. Furthermore, this suppression was antigen and disease specific. Most importantly, one CD8+ clone could reverse the ongoing disease. These new therapeutic approaches derived from animal models may offer a hope of more selective interventions for the treatment of human autoimmune diseases.