Characterization of inflammatory cells in autoimmune tubulointerstitial nephritis in rats

Brown Norway rats immunized with bovine tubular basement membrane (TBM) antigens develop tubulointerstitial nephritis. The composition of the inflammatory cell infiltrate was characterized in kidney tissue sections and cell suspensions obtained from affected kidneys. Anti-TBM antibody deposition in the kidney began 8 days after immunization and was followed on days 8 to 10 by C3 deposits and infiltration of polymorphonuclear leukocytes (PMN). After day 13, the infiltrate became almost exclusively mononuclear in character. On day 13, the inflammatory mononuclear cells recovered by Ficoll-Hypaque centrifugation contained 10% Ig+ cells (B cells), 60% W3/25+ cells (T helper cells), 9% OX8+ cells (T suppressor cells), 9% esterase+ cells (monocytes/macrophages), 4% renal cells, and 8% other unidentified cells. Monocytes/macrophages were prominent only at the latest stages of the disease. The ratio of W3/25+ to OX8+ cells was higher in the kidney than in the spleen or peripheral blood. The sequential accumulation of T cells and then monocytes/macrophages after an initial antibody, complement, and PMN lesion suggests a role for the T cells (selective prevalence of the helper T cell population over that of suppressor T cells) both as inflammatory cells and in progression and regulation of the subsequent stages of injury.