Cytolytic lymphocytes induce both apoptosis and necrosis in target cells.
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.
Zychlinsky
A
A
Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, NY 10021.
Zheng
L M
LM
Liu
C C
CC
Young
J D
JD
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003602:Cytotoxicity, Immunologic; D004249:DNA Damage; D003609:Dactinomycin / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000201:enzymology / Q000502:physiology*; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D008854:Microscopy, Electron; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011691:Puromycin / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology / Q000502:physiology*; D015032:Zinc / Q000494:pharmacology
D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D003609:Dactinomycin; D011691:Puromycin; D015032:Zinc