The role of lymphocytes in the progression of interstitial disease

Chronic interstitial disease is a major cause of end-stage renal failure. The process is characterized mainly by tubular atrophy and interstitial fibrosis and may be the result of primary or secondary interstitial nephritis. The secondary form attends almost all instances of progressive glomerular and vascular diseases, determining in a large part their outcome. Both forms of interstitial nephritis are initially characterized by the presence of mononuclear infiltrates with the majority being T lymphocytes. The predominance of CD4+ or CD8+ T-cells depends on the underlying cause. Both cell types may lead directly or indirectly to the induction of tubulointerstitial fibrosis. Direct stimulation of fibroblasts to proliferate and produce extracellular matrix may be caused by TGF-beta, IL-4, TNF-alpha, and other fibroblast stimulating factors. Indirect induction of fibroblasts is mediated by stimulation of monocytes/macrophages through IL-2 and IFN-gamma. Furthermore, T cells may directly interact with epithelial cells, leading, for example, to a decrease in type IV collagen production in these cells, thus contributing directly to tubular atrophy. The role of MHC class II expression on tubular epithelial cells in the process of chronic interstitial disease remains to be fully elucidated.