Reduction of mortality and lymphadenopathy in mrl‐lpr/lpr mice treated with nonmitogenic anti‐cd3 monoclonal antibody

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Abstract
Objective. To evaluate the therapeutic efficacy of nonmitogenic anti‐CD3 monoclonal antibody (MAb) in a preexisting autoaggressive response, using the MRL‐lpr/lpr (MRL/I) murine model of autoimmune disease. Methods. Female MRL/I 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 α/β+, 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 cytokinemediated 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.