Inhibition of Cytotoxic T Lymphocyte - induced Target Cell DNA Fragmentation , but Not Lysis , by Inhibitors of DNA Topoisomerases
نویسندگان
چکیده
Cytotoxic T lymphocytes (CTL) kill their target cells via a contact-dependent mechanism that results in the perturbation of the target cell's plasma membrane and the fragmentation of the target cell's DNA into nucleosomal particles. The membrane disruption is presumed to be due to the action of perforin, while the DNA fragmentation is thought to be by the activation of an endogenous nuclease(s). DNA topoisomerases I and II are nuclear enzymes with inherent endonuclease activities. We have investigated their role in the CTLinduced DNA fragmentation process. We report that in CTL killing assays, the treatment of target cells with topoisomerase I and II inhibitors blocks the CTL-induced DNA fragmentation process, but not the lysis of the target cell.
منابع مشابه
Inhibition of cytotoxic T lymphocyte-induced target cell DNA fragmentation, but not lysis, by inhibitors of DNA topoisomerases I and II
Cytotoxic T lymphocytes (CTL) kill their target cells via a contact-dependent mechanism that results in the perturbation of the target cell's plasma membrane and the fragmentation of the target cell's DNA into nucleosomal particles. The membrane disruption is presumed to be due to the action of perforin, while the DNA fragmentation is thought to be by the activation of an endogenous nuclease(s)...
متن کاملSusceptibility to cytotoxic T lymphocyte-induced apoptosis is a function of the proliferative status of the target
Cytotoxic T lymphocytes (CTL) kill cells by perturbing the target's plasma membrane and by inducing the disintegration of the target cell's DNA into oligonucleosomal fragments, a process characteristic of apoptosis. We show that the DNA fragmentation event is distinct from the membrane lysis event and is dependent on the state of target cell activation or commitment into the mitotic cycle. Quie...
متن کاملLack of lymphocyte-induced DNA fragmentation in human targets during lysis represents a species-specific difference between human and murine cells.
Significant cytotoxic lymphocyte-induced DNA fragmentation does not occur in four human target cells lysed by human natural killer lymphocytes, killer lymphocytes, or cytotoxic T lymphocytes. These results contrast with the extensive DNA fragmentation that occurs in murine target cells lysed by the analogous effector lymphocytes. Thus, DNA fragmentation, or the lack thereof, represents a specie...
متن کاملMechanism of killing by virus-induced cytotoxic T lymphocytes elicited in vivo.
The mechanism of lysis by in vivo-induced cytotoxic T lymphocytes (CTL) was examined with virus-specific CTL from mice infected with lymphocytic choriomeningitis virus (LCMV). LCMV-induced T cells were shown to have greater than 10 times the serine esterase activity of T cells from normal mice, and high levels of serine esterase were located in the LCMV-induced CD8+ cell population. Serine este...
متن کاملON THE EFFECTS OF ARA-A AND ARA-C ON X-RAY INDUCED DNA LESIONS IN NORMAL HUMAN AND A-T CELLS: SIMILARITIES AND DIFFERENCES.
A better understanding of the mechanism of chromosomal aberration formation could be obtained by using DNA repair inhibitors. Immortalized normal human (MRC 5 SVI) and ataxia telangiectasia ( AT 5 BIV A ) fibroblastic cell lines were treated with adenosine arabinoside (ara-A) and cytosine arabinoside (ara-C), both potent inhibitors of DNA dsb repair, alone or in combination with x-rays at ...
متن کامل