Structural observations on epithelioid and giant cells in experimental autoimmune tubulointerstitial nephritis in guinea pigs.

In order to analyze the role of phagocytic cells in experimental antitubular basement membrane (TBM) antibody-mediated nephritis, Hartley guinea pigs (GP) were immunized with rabbit tubular basement membrane (TBM) in complete Freund's adjuvant and pertussis vaccine. Renal tissue was obtained 10 to 15, 15 to 25, and 25 to 35 days after the start of immunization. Severe renal tubulointerstitial (RTI) nephritis developed in 95% of the animals. Linear deposits of IgG and C3 along TBM were seen 10 days after initial immunization. A few days later, monocytes and macrophages infiltrated the interstitium and subsequently differentiated into epithelioid and foreign body-type giant cells (GC). The GC were most actively involved in the destruction of the TBM: Cytoplasmic pseudopodia of the GC adhered to the TBM; the areas of membrane apposition were several microns in length; no evidence of specialization was found in the plasma membrane adjoining the TBM; no cellular organelles, except for abundant microfilaments, were seen in the contact regions. The initial contact was followed by lysis of plasma membrane of the GC and TBM, perforation of TBM, and phagocytosis of TBM fragments. Concomitantly, fluorescent staining for IgG along the TBM became discontinuous or disappeared. Destruction of TBM was accompanied by degeneration of tubular epithelial cells and collapse of tubular architecture. The morphologic observations are consistent with the hypothesis that, in GP, autoimmune RTI nephritis damage of TBM results from the cooperation of humoral and cellular mechanisms, probably akin to those of antibody-mediated lymphocytotoxicity.