Cellular and humoral mechanisms in the pathogenesis of tubulointerstitial nephritis.

Abstract

Brown-Norway (BN) rats immunized with renal medulla from Sprague-Dawley (SD) rats developed a renal lesion characterized by focal interstitial and perivascular mononuclear cell infiltrates without glomerular involvement. The cellular infiltrates were extracted from the affected kidneys and determined to consist of monocytes 64 +/- 4% (mean +/- S.D.) and T cells 2 +/- 9%. IgG antibodies directed at tubular basement membrane and tubular cell antigens were found in the affected kidneys and in circulation. Sera of immunized rats were used in in vitro studies to determine the presence of antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). In the CDC there was cytolysis of SD kidney and spleen cells but not BN kidney cells. In the ADCC there was significant lysis of BN kidney cells as well as SD kidney cells. Antibodies have been raised in the immunized rats against major histocompatibility (MHC) antigens as well as against autologous tubular cells. The finding of monocytes bearing Fc receptors among the infiltrating cells, as well as antibodies that can function in an ADCC indicates the presence of a combined immune effector mechanism that might be operative in tubulointerstitial nephritis.