Cytolytic lymphocytes induce both apoptosis and necrosis in target cells
- PMID: 1984450
Cytolytic lymphocytes induce both apoptosis and necrosis in target cells
Abstract
We examined the role of programmed cell death (apoptosis) in killer lymphocyte-mediated cytotoxicity. Two parameters of cell death, 51Cr release and DNA fragmentation, were assayed. Lymphokine-activated killer cell- or CTL-mediated death was inhibited in target cells where transcription or translation were blocked. Dying target cells showed ultrastructural changes typically associated with both apoptosis and necrosis. In contrast, target cells pretreated with macromolecular synthesis inhibitors and incubated with lymphokine-activated killer cells showed morphologic signs of necrosis only. Zn2+, an inhibitor of endonucleases, inhibited DNA fragmentation, but not 51Cr release in YAC-1 target cells, suggesting that the two effects can be dissociated. Finally, the cytotoxic effect of perforin, a pore-forming protein of killer lymphocytes that is known to cause necrotic death, was unaffected by the inhibition of either RNA or protein synthesis in target cells. Taken together, these results suggest that killer lymphocytes can induce both necrosis and apoptosis and that the two types of death can be dissociated with specific inhibitors.
Similar articles
-
DNA fragmentation induced by cytotoxic T lymphocytes can result in target cell death.Exp Cell Res. 1993 Jun;206(2):302-10. doi: 10.1006/excr.1993.1150. Exp Cell Res. 1993. PMID: 8500550
-
Dimethyl 2,2-dichlorovinyl phosphate (DDVP) markedly inhibits activities of natural killer cells, cytotoxic T lymphocytes and lymphokine-activated killer cells via the Fas-ligand/Fas pathway in perforin-knockout (PKO) mice.Toxicology. 2004 Nov 1;204(1):41-50. doi: 10.1016/j.tox.2004.05.019. Toxicology. 2004. PMID: 15369847
-
Increase in tumor necrosis factor-alpha mRNA but not perforin mRNA expression in response to two newly characterized anti-LFA-1 monoclonal antibodies.Nat Immun. 1994 Nov-Dec;13(6):301-14. Nat Immun. 1994. PMID: 7894201
-
Cellular mechanisms of lymphocyte-mediated lysis of tumor cells.Ann Ist Super Sanita. 1990;26(3-4):369-84. Ann Ist Super Sanita. 1990. PMID: 2151107 Review.
-
The mechanism of organophosphorus pesticide-induced inhibition of cytolytic activity of killer cells.Cell Mol Immunol. 2006 Jun;3(3):171-8. Cell Mol Immunol. 2006. PMID: 16893497 Review.
Cited by
-
A natural killer cell granule protein that induces DNA fragmentation and apoptosis.J Exp Med. 1992 Feb 1;175(2):553-66. doi: 10.1084/jem.175.2.553. J Exp Med. 1992. PMID: 1732416 Free PMC article.
-
Ca2+ signaling modulates cytolytic T lymphocyte effector functions.J Exp Med. 1998 Apr 6;187(7):1057-67. doi: 10.1084/jem.187.7.1057. J Exp Med. 1998. PMID: 9529322 Free PMC article.
-
Self major histocompatibility complex class I antigens expressed solely in lymphoid cells do not induce tolerance in the CD4+ T cell compartment.J Exp Med. 1996 Oct 1;184(4):1573-8. doi: 10.1084/jem.184.4.1573. J Exp Med. 1996. PMID: 8879232 Free PMC article.
-
Copy number loss in granzyme genes confers resistance to immune checkpoint inhibitor in nasopharyngeal carcinoma.J Immunother Cancer. 2021 Mar;9(3):e002014. doi: 10.1136/jitc-2020-002014. J Immunother Cancer. 2021. PMID: 33737344 Free PMC article.
-
Fas and tumor necrosis factor receptor-mediated cell death: similarities and distinctions.J Exp Med. 1994 Aug 1;180(2):557-67. doi: 10.1084/jem.180.2.557. J Exp Med. 1994. PMID: 7519240 Free PMC article.