Role of CD8+ cells in the progression of murine adriamycin nephropathy

Background. Many studies have shown that interstitial inflammation in human and experimental renal disease is characterized by T-cell infiltration, but published data on the involvement of inflammatory cell subsets in progressive tubulointerstitial lesions are often conflicting. A previous study suggested a role for cytotoxic T lymphocytes in the damaging effect of CD4(+) T-cell depletion in murine adriamycin (ADR) nephropathy, a model of focal segmental glomerulosclerosis (FSGS), and tubulointerstitial inflammation. The aim of this study was to investigate the role of CD8(+) cells in this model. Methods. Male BALB/c mice were treated with five intraperitoneal injections of anti-CD8 monoclonal antibody (mAb), beginning from five days after ADR treatment, when overt proteinuria was established. Seven mice in each of groups A (ADR + mAb), B (ADR only), and C (saline treated, age matched) were sacrificed at week 6. Changes in renal function and histopathological features were assessed. Tubulointerstitial inflammation and gromerular inflammation were examined immunohistochemically. Results. mAb treatment reduced CD8(+) cell levels to <2% of normal in spleen. Proteinuria in group A was no different from that in group B at week 6, but was markedly higher than in group C. Creatinine clearance was significantly ameliorated by anti-CDs treatment (71.8 +/- 4.9 <mu>L/min vs. 29.2 +/- 2.5 in group B and 81.9 +/- 3.7 in group C). Morphometric analysis showed less FSGS in group A compared with group B (6.5 +/- 1.9 vs. 13.0 +/- 2.8, P < 0.001), as well as less tubular atrophy (indicated by increased ratio of tubule cell height to tubular diameter, 0.25 +/- 0.24 in group A vs. 0.04 +/- 0.02 in group B, P < 0.05). CD8 depletion also reduced interstitial expansion (6.3 +/- 2.2% vs. 16.4 +/- 3.1 in group B, P < 0.001) and fibrosis (P < 0.01). Macrophage infiltration in tubulointerstitium was less in group A than in group B (P = 0.052). The number of interstitial CD4(+) cells appeared to increase after anti-CDs treatment, but was not statistically different between groups A and B. Conclusion. Anti-CD8 treatment protects against renal functional and structural injury in this murine model of chronic proteinuric renal disease.