In vivo treatment with a monoclonal antibody to T helper cells in experimental autoimmune glomerulonephritis in the BN rat

SUMMARY Experimental autoimmune glomerulonephritis (EAG) was induced in brown Norway (BN) rats by a single i.m. injection of homologous glomerular basement membrane (GBM) in Freund's complete adjuvant. This model of anti‐GBM disease is characterized by the development, over several weeks, of circulating and deposited anti‐GBM antibodies, accompanied by albuminuria. We examined the effects of treatment with MoAb W3/25 (anti‐CD4) at different doses, starting at the time of immunization and continued for the duration of the study or for a limited period only. Continued treatment with W3/25, at a dose of 5 or 10 mg/kg intraperitoneally three times per week for 4 weeks. produced a marked reduction in circulating anti‐GBM antibodies, absence of detectable deposited antibody and virtual absence of albuminuria. When W3/25 treatment, at 5 or 10 mg/kg, was stopped after 2 weeks, there was still a significant reduction in anti‐GBM antibodies and albuminuria at 4 weeks. A similar effect on the disease was achieved when W3/25 was administered only three times during the first week at a dose of 30 mg/kg. Animals injected with W3/25 at a dose of 10 mg/kg through the course of disease showed < 10% W3/25 + cells by KACS analysis of splenic lymphocytes at week 4, while controls and animals treated for shorter periods showed >30% W3 25 + cells. These results demonstrate that W3/25 can prevent the development of EAG and that this effect is not dependent on persistent depletion of T cells. Further work is necessary to determine whether anti‐T cell therapy is effective in established EAG and may be worth investigating in human anti‐GBM disease.