Anti-CD8 monoclonal antibody protects against spontaneous IgA nephropathy in ddY mice.
We investigated the effects of anti-CD4 monoclonal antibody (mAb) and/or anti-CD8 mAb in ddY mice, an animal model of spontaneous IgA nephropathy. Female ddY mice were treated with 18 intravenous injections of anti-CD4 and/or anti-CD8 mAb at 2-week intervals. This was based on our observation that a single injection of anti-CD4 mAb or anti-CD8 mAb caused a selective depletion in CD4+ T cells for 2 weeks and CD8+ T cells for 4 weeks, respectively. The level of proteinuria, serum IgA, and changes in the histopathological features of renal tissue samples were assessed in treated mice between the age of 4 and 40 weeks. The level of proteinuria increased with age, but there was not significant difference among the groups. No animal developed microhematuria throughout the study. Treatment with anti-CD4 mAb produced a mild to moderate level of mesangial hypertrophy at 20 and 40 weeks, similar to the results in untreated mice. The lowest degree of mesangial hypertrophy occurred in mice treated with anti-CD8 mAb up to the age of 40 weeks. Treatment with a combination of anti-CD4 and anti-CD8 mAbs produced effects that were similar to those observed on treatment with anti-CD8 mAb alone. Our results suggest that CD8+ T cells mediate mesangial proliferation and the progression of nephropathy in ddY mice.