CELL-MEDIATED IMMUNE INJURY IN THE KIDNEY - ACUTE NEPHRITIS INDUCED IN THE RAT BY AZOBENZENEARSONATE

Cell-mediated immune mechanisms have long been suspected of playing an important role in the pathogenesis of various renal diseases. An animal model of active nephritis secondary to an exogenous antigen that requires antigen presentation to immune-competent T cells has not been developed. Consequently, the potential of kidney cells to serve as effective antigen presenting cells after an exposure to a therapeutic, biological, or environmental agent in the intact animal has not been documented. The present experiments were designed to demonstrate the capacity of the kidney to become the target for cell-mediated immune injury. A model system has been developed whereby a chemically reactive form of the hapten azobenzenearsonate is introduced directly into the left kidney of pre-immunized Brown Norway rats. Previous studies have shown that this form of the hapten requires active antigen presentation but no intracellular processing, since the reactive form of the hapten modifies directly surface expressed proteins. Delayed hypersensitivity was demonstrated in the actively immunized animals by standard lymphocyte stimulation index and by in vivo skin testing. Peak foot pad swelling of 220 +/- 13 x 10(-2) mm in response to the hapten was observed between days 11 and 14 as compared to <10 x 10(-2) mm in the contralateral foot injected with vehicle alone and <20 x 10(-2) mm in response to azobenzenearsonate injection in animals immunized with adjuvant alone. The exposure of the kidney to the hapten in the primed animal results in an active unilateral granulomatous nephritis with marked destruction of tubules and glomeruli. On average, 71.5 +/- 5.2% of the renal cortex is affected by the inflammatory process in the actively immunized animals, compared to only 8.1 +/- 3.8% in controls. The disease can be reproduced qualitatively by adoptive transfer of T cells but not by passive antibody administration to naive recipients. These studies demonstrate that intrinsic kidney cells can act as effective antigen presenting cells in the intact animal and that the kidney can become the target of a cell-mediated immune injury.