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-C D3 monoclonal antibody (MAb) in a preexisting autoaggressive response, using the MRL-lpr/ lpr (MRL/I) murine model of autoimmune disease. Me thods. Female MRL/I mice, 8-10 weeks of age, were treated with nonmito genic anti-CD3 MAb or phosphate buffered saline and effects on mortali ty, lymphadenopathy, T cell phenotypes, anti-DNA titers, and total IgG titers were measured.Results. Nonmitogenic anti-CD3 MAb treatment res ulted in a dramatic reduction in lymphadenopathy and mortality, as wel l as an early reduction in alpha/beta+, CD4-, CD8-, Thy+, B220+ (doubl e-negative) lymph node cells. No significant effects on anti-DNA or Ig G titers were observed. No morbidity was observed following administra tion of nonmitogenic anti-CD3 MAb. Conclusion. A short course of treat ment with nonmitogenic anti-CD3 MAb can suppress preexisting autoimmun e responses without inducing the cytokine-mediated toxicity characteri stic of mitogenic forms of anti-CD3 MAb. The use of nonmitogenic anti- CD3 MAb may be efficacious in the clinical setting for the treatment o f T cell-mediated autoimmune disorders.