We investigated the effects of anti-CD4 monoclonal antibody (mAb) and/
or anti-CD8 mAb in ddY mice, an animal model of spontaneous IgA nephro
pathy. 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 ou
r observation that a single injection of anti-CD8, mAb or anti-CD8 mAb
caused a selective depletion in CD4+ T cells for 2 weeks and CD8+ T c
ells for 4 weeks, respectively. The level of proteinuria, serum IgA, a
nd changes in the histopathological features of renal tissue samples w
ere assessed in treated mice between the age of 4 and 40 weeks. The le
vel of proteinuria increased with age, but there was not significant d
ifference among the groups. No animal developed microhematuria through
out the study. Treatment with anti-CD4 mAb produced a mild to moderate
level of mesangial hypertrophy at 20 and 40 weeks, similar to the res
ults in untreated mice. The lowest degree of mesangial hypertrophy occ
urred in mice treated with anti-CD8 mAb up to the age of 40 weeks. Tre
atment with a combination of anti-CD4 and anti-CD8 mAbs produced effec
ts that were similar to those observed on treatment with anti-CD8 mAb
alone. Our results suggest that CD8+ T cells mediate mesangial prolife
ration and the progression of nephropathy in ddY mice.