Crucial role of CD8-positive lymphocytes in glomerular expression of ICAM-1 and cytokines in crescentic glomerulonephritis of WKY rats.

CD8-positive lymphocytes (CD8+ lym) and ICAM-1/LFA-1 interaction have been implicated in the glomerular accumulation of monocytes/macrophages (Mo/Mphi) and crescent formation in antiglomerular basement membrane (anti-GBM) glomerulonephritis of WKY rats. In the present study, the role of CD8+ lym in the expression of ICAM-1 and inflammatory cytokines as well as in the accumulation of Mo/Mphi in the glomeruli was examined by RNase protection assay and immunofluorescence microscopy. ICAM-1 expression was apparent at 1 h and markedly enhanced at day 3 in glomeruli after an anti-GBM Ab injection in parallel with glomerular accumulation of Mo/Mphi. Expression of mRNA for IL-1beta, TNF-alpha, and IFN-gamma, known to enhance ICAM-1 expression, and MIP-1alpha, MIP-1beta, and MCP-1, known to activate leukocyte integrins or to act as chemokines, were also induced in the glomeruli at a mRNA level in a profile similar to that of ICAM-1 expression. By depleting the CD8+ lym in the circulation, the increased glomerular expression of ICAM-1 and the cytokines, except IL-1beta, and the Mo/Mphi accumulation were suppressed, indicating a crucial role of CD8+ lym in the accumulation of Mo/Mphi through stimulation of ICAM-1 and induction of cytokines.