Reduction of mortality and lymphadenopathy in MRL-lpr/lpr mice treated with nonmitogenic anti-CD3 monoclonal antibody.

OBJECTIVE To evaluate the therapeutic efficacy of nonmitogenic anti-CD3 monoclonal antibody (MAb) in a preexisting autoaggressive response, using the MRL-lpr/lpr (MRL/l) murine model of autoimmune disease. METHODS Female MRL/l mice, 8-10 weeks of age, were treated with nonmitogenic anti-CD3 MAb or phosphate buffered saline and effects on mortality, lymphadenopathy, T cell phenotypes, anti-DNA titers, and total IgG titers were measured. RESULTS Nonmitogenic anti-CD3 MAb treatment resulted in a dramatic reduction in lymphadenopathy and mortality, as well as an early reduction in alpha/beta+, CD4-, CD8-, Thy+, B220+ (double-negative) lymph node cells. No significant effects on anti-DNA or IgG titers were observed. No morbidity was observed following administration of nonmitogenic anti-CD3 MAb. CONCLUSION A short course of treatment with nonmitogenic anti-CD3 MAb can suppress preexisting autoimmune responses without inducing the cytokine-mediated toxicity characteristic of mitogenic forms of anti-CD3 MAb. The use of nonmitogenic anti-CD3 MAb may be efficacious in the clinical setting for the treatment of T cell-mediated autoimmune disorders.