Depletion of CD4(+) T cells aggravates glomerular and interstitial injury in murine adriamycin nephropathy

Background. CD4(+) T cells play an important role in various types of immun ologic renal disease, including lupus nephritis, IgA nephropathy, and cresc entic glomerulonephritis. CD4(+) T cells are also major infiltrating lympho cytes in chronic tubulointerstitial inflammation associated with nonimmunol ogical renal diseases. We suspected that CD4(+) T cells might contribute to disease progression and loss of renal function in chronic proteinuric rena l disease (CPRD). To investigate this possibility, the effect of monoclonal antibody against CD4(+) lymphocytes (anti-CD4) was studied in a murine mod el (adriamycin nephropathy) of CPRD. Methods. Adriamycin nephropathy was produced in male BALB/c mice by a singl e intravenous injection of adriamycin (11 mg/kg). Anti-CD4 was given by int raperitoneal injection following the development of proteinuria at days 5, 6, 7, 21, and 37 after adriamycin. After six weeks, renal function and hist ology were studied by histomorphometry, immunohistochemistry, and flow cyto metry. Results. Flow cytometric analysis showed a marked decrease in the number of CD4(+) T cells in blood and spleen of the antibody-treated animals (N = 7, P < 0.01). Adriamycin plus CD4(+) depletion mice had significantly greater mesangial expansion, glomerular sclerosis, and interstitial expansion than the mice on adriamycin alone. Interstitial infiltration with macrophages a nd CD8(+) cells was significantly increased in adriamycin plus CD4(+) deple tion mice. Creatinine clearance (17.5 +/- 0.54 vs. 29.2 +/- 0.89 <mu>L/min, P < 0.001) was significantly worse in the adriamycin plus CD4(+) depletion mice than in adriamycin alone mice and correlated with histologic change i n glomeruli and interstitium. Conclusions. Depletion of CD4(+) T cells promotes glomerular and interstiti al injury in mice with established adriamycin nephropathy. These findings s uggest that CD4(+) T cells have a protective role against the progression o f adriamycin nephropathy.