T-cell mediated cytolysis: evidence for target-cell suicide.
The mechanism by which cytotoxic T-lymphocytes (Tc) induce the death of specific target cells is still controversial. We have used quantitative cytochemical methods to distinguish the metabolic activities of the target cells from those of the Tc, even when they are attached to each other. Early events following Tc-P8(15) target cell interaction were first, increased glucose 6-phosphate dehydrogenase activity and second, labilization of the lysosomes within the target cell: these changes could be mimicked, in part, by polyamines and could be inhibited by inhibiting ornithine decarboxylase (ODC) activity. The crucial role of ODC in the chain of events that led to cytolysis in this particular experimental system was shown first, by measuring ODC activity directly and secondly, by the inhibition of cytolysis by the presence of a selective inhibitor of ODC activity.
Division of Cellular Biology, Mathilda and Terence Kennedy Institute of Rheumatology, London, UK.
J
J
Chayen
A A
AA
Pitsillides
L
L
Bitensky
I H
IH
Muir
P M
PM
Taylor
B A
BA
Askonas
D000818:Animals; D002450:Cell Communication; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D000518:Eflornithine / Q000494:pharmacology; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D051379:Mice; D009955:Ornithine Decarboxylase / Q000502:physiology*; D011073:Polyamines / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*
D011073:Polyamines; D005954:Glucosephosphate Dehydrogenase; D009955:Ornithine Decarboxylase; D000518:Eflornithine