EARLY STEPS IN SPECIFIC TUMOR-CELL LYSIS BY SENSITIZED MOUSE T LYMPHOCYTES .2. ELECTROLYTE PERMEABILITY INCREASE IN TARGET-CELL MEMBRANE CONCOMITANT WITH PROGRAMMING FOR LYSIS

Abstract

In a previous study of the mechanism of specific target cell lysis by alloimmune cytolytic T [thymus-derived] lymphocytes (CTL), the target cell became irreversibly programmed to lyse within a few minutes after contact with the CTL. In this paper it was shown that at each point in time, the level of specific release of the K analog, 86Rb, equals the percentage of target cells [mouse mastocytoma P815 cells] programmed to lyse. Specific release of 86Rb is more rapid than that of a small metabolite of similar weight, 14C-nicotinamide, which is specifically released more rapidly than 51Cr. Thus, an electrolyte-permeable lesion is produced in the target cell membrane within minutes of contact with the CTL. Since measurements of 86Rb release, unlike measurements of programming for lysis, do not involve exposure of the cells to EDTA and vigorous shearing forces, these results show that the CTL effects crucial and irreversible changes in the target cell within minutes after contact. The 1st, and perhaps only damage administered directly by the CTL, is probably a membrane lesion permeable to electrolytes and possibly to small molecules.