Mechanisms of immune lysis. III. Characterization of the nature and kinetics of the cytotoxic T lymphocyte-induced nuclear lesion in the target.

The experiments reported here demonstrate that the event leading to CTL-induced nuclear disintegration is kinetically similar (t1/2 = 3.1 +/- 0.8 min) to that reported for CTL-induced plasma membrane disintegration as measured by 51Cr release. However, the expression of the lethal event by detergent-soluble 125I release occurs so rapidly that the time between the initiation of the lesion and its expression is 15 min instead of the 90 to 120 min time course for plasma membrane disintegration measured by 51Cr release. In addition, we have demonstrated that the rapid 125IUdR release characteristic of CTL-lysed targets is specific for the nucleus within the target cell itself. Isolated nuclei cultured with effectors and targets during a lytic reaction are not rapidly damaged by the lytic process. Finally, we have characterized the CTL-induced nuclear lesion as a degradative process occurring within the plasma membrane of the target cell. The significance of these events and their relationship to the CTL's role in the host defense system is discussed.