Effect of cyclosporin A on the non-MHC endothelial antibody response in the rat

The effect of cyclosporin A (CsA) on the in vivo humoral immune response against the non-MHC endothelial antigen that is present on the renal capillary and venous endothelium was tested in a rat model. Male MAXX rats were immunized using pooled spleen and lymph node cells from MHC-identical Brown Norway rats to induce the endothelial antibody response. The animals were treated with different doses of CsA for different periods and it was found that CsA suppressed the response completely and irreversibly when administered in a dose of 15 mg/kg/day with a minimum duration of therapy for 2 weeks. Animals that received a lower dose (10 mg/kg/day) or 15 mg/kg/day for 1 week, did show an initial response but failed to respond after repeated immunizations. The results show that CsA suppresses the humoral response to non-MHC alloantigens. Furthermore, a state of nonresponsiveness appears to be induced with doses which are not effective in suppressing the initial antibody response.