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

Role of CD8+ cells in the progression of murine adriamycin nephropathy.BackgroundMany 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.MethodsMale 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 glomerular inflammation were examined immunohistochemically.ResultsmAb 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-CD8 treatment (71.8 ± 4.9 μL/min vs. 29.2 ± 2.8 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-CD8 treatment, but was not statistically different between groups A and B.ConclusionAnti-CD8 treatment protects against renal functional and structural injury in this murine model of chronic proteinuric renal disease