Lymphocytes are dispensable for glomerulonephritis but required for renal interstitial fibrosis in matrix defect-induced Alport renal disease

One current theory for the emergence of glomerular nephritis implicates Th1-type cellular responses associated with delayed-type hypersensitivity, involving T cells and macrophages. Using a mouse model for progressive glomerulonephritis, we investigate the role of B and T cells in the pathogenesis of glomerular inflammation. Deletion of alpha 3 chain of type IV collagen in mice (alpha 3( IV) collagen null mice) results in GBM defects, glomerulonephritis and tubulointerstitial inflammation, fibrosis and significant immune infiltration including activated B- and T-lymphocytes. To evaluate the contribution of lymphocytes to the pathogenesis of glomerulonephritis and renal fibrosis, we generated mice that are deficient in both the alpha 3( IV) collagen and Rag-1 (alpha 3/Rag-1 DKO). Lymphocyte deficiency significantly reduces fibrosis in the renal interstitium, but ultrastructural GBM defects persist. Interestingly, glomerulonephritis in the double null mice persists at a similar level with comparable proteinuria. Here we demonstrate that despite the presence of B- cell and T-cells in the inflamed glomeruli, their deletion does not impede the emergence of glomerulonephritis but has a negative impact on the progression of renal interstitial fibrosis.