EFFECT OF NOVEL IMMUNOSUPPRESSIVE AGENT, FK506, ON THE INDUCTION OF EXPERIMENTAL GLOMERULONEPHRITIS

Abstract

We studied the effect of a novel immunosuppressive agent, FK506, on two models of experimental glomerulonephritis. The induction of active Heymann nephritis was completely suppressed by FK506 injected simultaneously with the antigen (day 1) and successively daily for 14 days at a dose of 0.64 mg/kg per day or more. With a lower dosage or other treatment schedules (for 1-7 days or for day 8-21 days duration), immune deposits in the glomerular basement membrane (GBM) occurred despite the suppression of proteinuria. Rats that were prevented from developing Heymann nephritis or the autologous phase of Masugi nephritis by FK506 treatment exhibited a suppressed immune response to a second immunization with the same antigen even 4 weeks after cessation of drug administration ; however, they developed antibodies and immune deposits in the GBM when inoculated with other antigens. In vitro, antibody production of lymphocytes from nephritic rats was suppressed when co-cultured with T lymphocytes from FK506-treated Heymann nephritic rats.
These results indicate that FK506 has potent immunosuppressive activity, and suggest that FK506 is able to induce an antigen-specific immunotolerance maintained by suppressor T cells.