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

Counteracting the effect of autoimmunity can be achieved by eliminatio n or inactivation of autoreactive T cells. We have focused on two appr oaches targeting on autoaggressive T cells in the model of collagen-in duced arthritis (CIA) in mice. First, type II collagen (CII) primed DB A /1 mice were treated with various monoclonal antibodies (mAb) specif ic for the beta chains of the T cell receptor (TCR) using a protocol r esulting 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-reg ulated by that of anti-Vbeta2 and/or anti-Vbeta5, presumably by deleti ng pathogenic T cell clones. In contrast, treatment with either antiVb eta6 or anti-Vbeta11 mAb did not alter CIA. Second, we generated CII-s pecific T cell hybrid clones that recognize the antigenic peptides in association with K(q) and IA(q) molecules respectively for CD8+ and CD 4+ cells. Vaccination with the irradiated hybrid clones, 3 weeks prior to immunization, was effective in preventing the development of arthr itis. Furthermore, this suppression was antigen and disease specific. Most importantly, one CD8+ clone could reverse the ongoing disease. Th ese new therapeutic approaches derived from animal models may offer a hope of more selective interventions for the treatment of human autoim mune diseases.