Cytotoxic T lymphocytes induce different types of DNA damage in target cells of different origins.
Nuclear changes may be important in the mechanism of CTL-mediated lysis. Rapid cleavage of target cell DNA into oligonucleosomes has been demonstrated as a very early event in CTL-mediated killing of murine hematopoietic targets. However, the results presented herein and by other investigators have shown that this extensive dsDNA fragmentation does not occur in all CTL targets. In terms of actual DNA damage, there is a wide range in the extent and type of DNA cleavage in various targets. Differences exist at both the species and the cell lineage level. The extent of DNA damage generally corresponds to the efficiency of lysis; thus, murine hematopoietic cells, which undergo dsDNA fragmentation, are killed more rapidly and at lower E/T cell ratios than are murine nonhematopoietic cells, which sustain single-stranded nicks. Experiments using cloned CTL demonstrate that the same effector cell kills both hematopoietic and nonhematopoietic targets, producing different types of DNA damage. These observations indicate that the fate of the target cell DNA is determined by the nature of the target cell and not by the CTL. We propose that DNA damage results from an enzyme pathway inherent to the target, which is activated by, not transferred from, the CTL.
Sellins
K S
KS
Department of Microbiology and Immunology, University of Colorado Medical School, Denver 80262.
Cohen
J J
JJ
D000818:Animals; D001386:Azides / Q000494:pharmacology; D003165:Complement System Proteins / Q000494:pharmacology; D006224:Cricetinae; D003602:Cytotoxicity, Immunologic / Q000235:genetics*; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D004139:Dinitrofluorobenzene / Q000494:pharmacology; D004587:Electrophoresis, Agar Gel; D005615:Freezing; D006358:Hot Temperature / Q000009:adverse effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D019810:Sodium Azide; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*
D001386:Azides; D003165:Complement System Proteins; D004247:DNA; D019810:Sodium Azide; D004139:Dinitrofluorobenzene