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

Abstract

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 FACS 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.