DNA fragmentation: manifestation of target cell destruction mediated by cytotoxic T-cell lines, lymphotoxin-secreting helper T-cell clones, and cell-free lymphotoxin-containing supernatant.
- 1 March 1986
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 83 (6) , 1881-1885
- https://doi.org/10.1073/pnas.83.6.1881
Abstract
A Lyt-2+, trinitrophenyl-specific, lymphotoxin-secreting, cytotoxic T-cell line, PCl 55, mediates the digestion of target cell DNA into discretely sized fragments. This phenomenon manifests itself within 30 min after effector cell encounter as measured by the release of 3H counts from target cells prelabeled with [3H]deoxythymidine and occurs even at very low effector to target cell ratios (0.25:1). A Lyt-1+, ovalbumin-specific, lymphotoxin-secreting T-helper cell clone, 5.9.24, is also able to mediate fragmentation of target cell DNA over a time course essentially indistinguishable from the cytotoxic T lymphcyte-mediated hit. Cell-free lymphotoxin-containing supernatants also cause release of DNA from targets, although they require a longer time course, on the order of 24 hr. In contrast, lysis of cells by antibody plus complement or Triton X-100 does not result in DNA release even after extended periods of incubation (24 hr). All three treatments that result in the release of DNA from cells cause fragmentation of that DNA into discretely sized pieces that are multiples of 200 base pairs. The results thus suggest that cytotoxic T cells, lymphotoxin-secreting helper clones with cytolytic activity, and lymphotoxin all effect target cell destruction by means of a similar mechanism and that observed differences in time course and the absence of target cell specificity in killing mediated by lymphotoxin may simply reflect differences in the mode of toxin delivery.This publication has 27 references indexed in Scilit:
- A comparison of lysis mediated by Lyt 2+ TNP-specific cytotoxic-T-lymphocyte (CTL) lines with that mediated by rapidly internalized lymphotoxin-containing supernatant fluids: Evidence for a role of soluble mediators in CTL-mediated killingCellular Immunology, 1985
- Liposomes as targets for granule cytolysin from cytotoxic large granular lymphocyte tumors.Proceedings of the National Academy of Sciences, 1984
- Cytolytic activity of purified cytoplasmic granules from cytotoxic rat large granular lymphocyte tumors.The Journal of Experimental Medicine, 1984
- Cloned helper T cells can kill B lymphoma cells in the presence of specific antigen: Ia restriction and cognate vs. noncognate interactions in cytolysisEuropean Journal of Immunology, 1984
- Cytolysis by H-2-specific T killer cells. Assembly of tubular complexes on target membranes.The Journal of Experimental Medicine, 1983
- Introduction of macromolecules into cultured mammalian cells by osmotic lysis of pinocytic vesiclesCell, 1982
- MHC-Restricted Cytotoxic T Cells: Studies on the Biological Role of Polymorphic Major Transplantation Antigens Determining T-Cell Restriction-Specificity, Function, and ResponsivenessPublished by Elsevier ,1979
- Cell-Mediated Cytotoxicity, Allograft Rejection, and Tumor ImmunityPublished by Elsevier ,1974
- Binding of Human Lymphotoxin to Target-Cell Membranes and Its Relation to Cell-Mediated CytodestructionProceedings of the National Academy of Sciences, 1973
- CYTOTOXICITY MEDIATED BY SOLUBLE ANTIGEN AND LYMPHOCYTES IN DELAYED HYPERSENSITIVITYThe Journal of Experimental Medicine, 1968