Intercellular interactions in the interphase death of irradiated thymocytes

The effect of the interaction of different types of cells on the interphase death and pycnosis of thymocytes irradiated in vitro was studied. When removed from the thymus suspension of cells with natural killer activity, medullary thymocytes and macrophages did not change the radiation-induced death of cortical thymocytes. On the other hand, postirradiation incubation of cortical thymocytes together with unirradiated thymocytes or with cells of certain other cell lines diminished thymocyte death. Mixing the cell suspensions and changing the incubation medium decreased thymocyte death. All of these results indicate that these cells produce soluble mediators that are toxic to the cells that secrete them. The possible nature of these autotoxic mediators has been studied using inhibitors of arachidonic acid metabolism. Inhibitors of phospholipase A2 or lipoxygenase reduced interphase death markedly, while an inhibitor of cyclooxygenase did not. These data suggest that some lipoxygenase products may serve as autotoxic mediators in the interphase death of thymocytes.