M. Henrickson et al., REDUCTION OF MORTALITY AND LYMPHADENOPATHY IN MRL-LPR LPR MICE TREATED WITH NONMITOGENIC ANTI-CD3 MONOCLONAL-ANTIBODY/, Arthritis and rheumatism, 37(4), 1994, pp. 587-594
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.