THE ROLE OF LYMPHOCYTES IN THE PROGRESSION OF INTERSTITIAL DISEASE

Chronic interstitial disease is a major cause df end-stage renal failu re. The process is characterized mainly by tubular atrophy and interst itial fibrosis and may be the result of primary or secondary interstit ial nephritis. The secondary form attends almost all instances of prog ressive glomerular and vascular diseases, determining in a large part their outcome. Both forms of interstitial nephritis are initially char acterized by the presence of mononuclear infiltrates with the majority being T lymphocytes. The predominance of CD4(+) or CD8(+) T-cells dep ends on the underlying cause. Both cell types may lead directly or ind irectly to the induction of tubulointerstitial fibrosis. Direct stimul ation of fibroblasts to proliferate and produce extracellular matrix m ay be caused by TGF-beta, IL-4, TNF-alpha, and other fibroblast stimul ating factors. Indirect induction of fibroblasts is mediated by stimul ation of monocytes/macrophages through IL-2 and IFN-gamma. Furthermore , T cells may directly interact with epithelial cells, leading, for ex ample, to a decrease in type IV collagen production in these cells, th us contributing directly to tubular atrophy. The role of MHC class II expression on tubular epithelial cells in the process of chronic inter stitial disease remains to be fully elucidated.