Nuclear disintegration induced by cytotoxic T lymphocytes. Evidence against damage to the nuclear envelope of the target cell

Abstract

CTL and NK cells induce nuclear disintegration in their target cells. This phenomenon, which is seen as extensive fragmentation and solubilization of target cell DNA, is not seen with most other means of inducing cytolysis, including antibody- and complement-mediated cytolysis. We have previously shown that the degree of DNA solubilization is dependent upon the nature of the target cell. We here investigate the possibility that CTL induce, in all targets, damage to the nuclear envelope, which in turn leads to nuclear disintegration in only some of them. We reasoned that damage to the nuclear envelope would render nuclear DNA more accessible to exogenous DNase. Therefore, we determined the susceptibility of target DNA to exogenous DNase I after cytolysis by various means. We found no difference in DNA susceptibility for cells lysed by CTL vs methods (such as complement-mediated lysis or nonionic detergent) incapable of inducing nuclear disintegration. As a positive control, freezing and thawing dramatically enhanced susceptibility of the DNA. In conclusion, we found no evidence that the nuclear envelope is damaged by CTL in target cell types (or in the subpopulation of nuclei) that do not undergo nuclear disintegration.