Renal epithelium: reversal of cytotoxic damage by addition of anti-thymocyte globulin

A novel in vitro assay of renal epithelium tight junction function was used to assess the efficacy with which rabbit anti-thymocyte globulin (ATG) blocks epithelium damage mediated by lymphokine-activated killer (LAK) cells. It was found that LAK cells lysed renal epithelial cells poorly in standard chromium-release assays but that they caused a rapid, and almost total, reduction in trans-epithelium monolayer resistance, indicating tight junction failure and, hence, loss of tissue function. LAK cell-mediated cytolysis of the sensitive K562 cell line was completely blocked in the presence of ATG at a concentration of 200 g/ml. Addition of ATG at this concentration to damaged renal cell monolayers in the presence of LAK cells allowed the trans-monolayer resistance to recover rapidly to levels approaching the values recorded before initial addition of LAK cells. On this basis it seems likely that the rapid restoration of renal function frequently observed after appropriate rescue therapy during episodes of acute rejection may reflect subtle changes in tissue function rather than recovery from widespread graft cell cytolysis.