Contribution of ED-1- and CD-8-positive cells to the development of crescentic-type anti-GBM nephritis in rats.

The current studies were designed to identify which mononuclear leukocytes have an important role in the development of glomerular injury using rats with original-type (mild injury) and crescentic-type (severe injury) anti-glomerular basement membrane (GBM) nephritis. 1) Proteinuria was persistent in crescentic-type anti-GBM nephritis compared with original-type anti-GBM nephritis. Macrophages/monocytes (ED-1), cytotoxic/suppressor T cells (CD-8), interleukin-2-receptor (CD-25)-positive cells and Ia-positive cells accumulated remarkably and persisted for longer in crescentic-type nephritic glomeruli. 2) We then performed investigations using immunosuppressants. Cyclosporin A abrogated proteinuria more effectively than azathioprine in crescentic-type nephritis. However, plasma antibody titer and glomerular rat IgG deposition were equally reduced by both azathioprine and cyclosporin A. The increase in the numbers of ED-1-, CD-8- and CD-25-positive cells in nephritic glomeruli was completely inhibited by cyclosporin A, but inhibited only slightly by azathioprine. 3) There was a correlation between the degree of proteinuria and the number of ED-1- and CD-8-positive cells. It is likely that these cells are leukocytes that lead to glomerular injury in nephritis. 4) In additional experiments using monoclonal antibodies against macrophages/monocytes and cytotoxic/suppressor T cells, urinary protein excretion and accumulation of these cells were blunted in nephritic rats treated with these antibodies. These results suggest that ED-1- and CD-8-positive cells are involved in the development of crescentic-type anti-GBM nephritis.