Lymphokine-activated killer (LAK) activity to cultured rat kidney parenchymal components in vitro

Abstract. The susceptibility of cultured rat kidney parenchymal components to natural killer (NK) cell and lymphokine-activated killer (LAK) cell-mediated lysis in a 4-h in vitro ⁵¹chromium assay was investigated. Large granular lymphocytes (LGL) in the spleen and in the kidney allograft were able to lyse YAC cells during rejection, but they did not damage target endothelial, glomerular mesangial, glomerular epithelial, or tubular cells in resting state. Stimulation of the target cells with gamma-interferon - known to induce MHC (class II) antigens on the target cell surface - did not make the target cells susceptible to NK-mediated lysis. LAK cells generated by a 3-day incubation with interleukin-2 (IL-2) effectively lysed both YAC and P815 target cell lines. LAK cells were also slightly cytotoxic to all tested parenchymal target components in resting state. Gamma-interferon treatment of the cultured parenchymal cells prior to the chromium release assay, however, reduced LAK-mediated parenchymal cell cytotoxicity to nearly nondetectable levels. Obviously, many lymphokines, including IL-2 and gamma-interferon, are produced during rejection at the site of inflammation. This might induce the generation of LAK cells in situ as the lymphokines induce the production of MHC antigens in the graft. We interpret these findings as indicating that regardless of the generation of LAK, the protective effect of gamma-interferon neutralizes the LAK effect, and we suggest that neither LGL nor LAK cells play any essential role in rat kidney allograft rejection.