This investigation is concerned with the detailed mechanisms of cytotoxicity, and in particular, with early cell surface and intracellular events that occur upon the binding of a cytotoxic effector cell to its susceptible target. In earlier studies, we have shown by immunofluorescence microscopy that when cloned natural killer (NK) and cytolytic T lymphocyte (CTL) cells bind to susceptible target cells, a rapid and coordinate reorientation of the perinuclear Golgi apparatus and the microtubule-organizing center (MTOC) occurs inside the effector cell so that the two organelles face the bound target. It was proposed that the purpose served by this reorientation is to direct Golgi-derived secretory vesicles, containing one or more cytotoxic components, to the area of target cell binding. In order to establish more firmly that this reorientation of the two organelles is an essential early event in cytotoxicity, we have performed three different types of experiments. 1) Upon binding cloned effector cells to susceptible targets in the presence of Mg+2 but absence of Ca+2, conditions in which no killing occurs, we found that no reorientation of the MTOC in the effector cell is induced; however, the addition of Ca+2 to these cell couples results in a rapid MTOC reorientation. 2) With a lysis-defective subclone derived from a cytolytic NK clone, binding to target cells did not induce an MTOC reorientation in the defective killer cell. 3) In multitarget conjugates formed with single CTL, the MTOC in the CTL was oriented to face that one target cell which was in the process of lysis at the time. These results, together with our earlier findings, strongly indicate that a Golgi/MTOC reorientation inside the target-bound effector cells is a prerequisite for the effective lysis of the target. They also reveal the existence, previously unrecognized, of a specific signaling mechanism from the viable target cell to the effector cell, which must be involved in the triggering of this Golgi/MTOC reorientation. These conclusions are consistent with the proposal that a polar cytotoxic secretory mechanism is responsible for target cell lysis.
|Original language||English (US)|
|Number of pages||13|
|Journal||Journal of Molecular and Cellular Immunology|
|State||Published - 1985|
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