G. Chiocchia et al., T-CELL-TARGETED IMMUNOTHERAPY IN MURINE COLLAGEN-INDUCED ARTHRITIS, Clinical and experimental rheumatology, 11, 1993, pp. 190000015-190000017
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.