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. 1991 Mar 1;173(3):681–686. doi: 10.1084/jem.173.3.681

T cell-T cell killing is induced by specific epitopes: evidence for an apoptotic mechanism

PMCID: PMC2118827  PMID: 1705281

Abstract

Epstein-Barr virus-specific cytotoxic T lymphocyte clones were shown to be an effective target for their own lysis when incubated in the presence of their specific epitopes but not in the presence of irrelevant epitopes. The mode of cell killing appeared to be by apoptosis and was prevented by previously described inhibitors of the process. Degranulation, as measured by serine esterase activity, was involved in this form of T cell-T cell killing. This is the first report of T cell-T cell killing by apoptosis and is only observed in the presence of a specific epitope. This result may be of significance in the use of peptide-based vaccines.

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Selected References

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  1. Baxter G. D., Collins R. J., Harmon B. V., Kumar S., Prentice R. L., Smith P. J., Lavin M. F. Cell death by apoptosis in acute leukaemia. J Pathol. 1989 Jun;158(2):123–129. doi: 10.1002/path.1711580207. [DOI] [PubMed] [Google Scholar]
  2. Berke G. Cytotoxic T-lymphocytes. How do they function? Immunol Rev. 1983;72:5–42. doi: 10.1111/j.1600-065x.1983.tb01071.x. [DOI] [PubMed] [Google Scholar]
  3. Berke G., Rosen D. Are lytic granules and perforin 1 involved in lysis induced by in vivo-primed peritoneal exudate cytolytic T lymphocytes? Transplant Proc. 1987 Feb;19(1 Pt 1):412–416. [PubMed] [Google Scholar]
  4. Berke G., Rosen D. Highly lytic in vivo primed cytolytic T lymphocytes devoid of lytic granules and BLT-esterase activity acquire these constituents in the presence of T cell growth factors upon blast transformation in vitro. J Immunol. 1988 Sep 1;141(5):1429–1436. [PubMed] [Google Scholar]
  5. Blakely A., Gorman K., Ostergaard H., Svoboda K., Liu C. C., Young J. D., Clark W. R. Resistance of cloned cytotoxic T lymphocytes to cell-mediated cytotoxicity. J Exp Med. 1987 Oct 1;166(4):1070–1083. doi: 10.1084/jem.166.4.1070. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Burrows S. R., Misko I. S., Sculley T. B., Schmidt C., Moss D. J. An Epstein-Barr virus-specific cytotoxic T-cell epitope present on A- and B-type transformants. J Virol. 1990 Aug;64(8):3974–3976. doi: 10.1128/jvi.64.8.3974-3976.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Burrows S. R., Sculley T. B., Misko I. S., Schmidt C., Moss D. J. An Epstein-Barr virus-specific cytotoxic T cell epitope in EBV nuclear antigen 3 (EBNA 3). J Exp Med. 1990 Jan 1;171(1):345–349. doi: 10.1084/jem.171.1.345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dennert G., Landon C., Nowicki M. Cell-mediated and glucocorticoid-mediated target cell lysis do not appear to share common pathways. J Immunol. 1988 Aug 1;141(3):785–791. [PubMed] [Google Scholar]
  9. Duke R. C., Chervenak R., Cohen J. J. Endogenous endonuclease-induced DNA fragmentation: an early event in cell-mediated cytolysis. Proc Natl Acad Sci U S A. 1983 Oct;80(20):6361–6365. doi: 10.1073/pnas.80.20.6361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Henkart P. A. Mechanism of lymphocyte-mediated cytotoxicity. Annu Rev Immunol. 1985;3:31–58. doi: 10.1146/annurev.iy.03.040185.000335. [DOI] [PubMed] [Google Scholar]
  11. Jiang S. B., Persechini P. M., Zychlinsky A., Liu C. C., Perussia B., Young J. D. Resistance of cytolytic lymphocytes to perforin-mediated killing. Lack of correlation with complement-associated homologous species restriction. J Exp Med. 1988 Dec 1;168(6):2207–2219. doi: 10.1084/jem.168.6.2207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kranz D. M., Eisen H. N. Resistance of cytotoxic T lymphocytes to lysis by a clone of cytotoxic T lymphocytes. Proc Natl Acad Sci U S A. 1987 May;84(10):3375–3379. doi: 10.1073/pnas.84.10.3375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Masson D., Nabholz M., Estrade C., Tschopp J. Granules of cytolytic T-lymphocytes contain two serine esterases. EMBO J. 1986 Jul;5(7):1595–1600. doi: 10.1002/j.1460-2075.1986.tb04401.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Miller S. A., Dykes D. D., Polesky H. F. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988 Feb 11;16(3):1215–1215. doi: 10.1093/nar/16.3.1215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Moss D. J., Misko I. S., Burrows S. R., Burman K., McCarthy R., Sculley T. B. Cytotoxic T-cell clones discriminate between A- and B-type Epstein-Barr virus transformants. Nature. 1988 Feb 25;331(6158):719–721. doi: 10.1038/331719a0. [DOI] [PubMed] [Google Scholar]
  16. Nagler-Anderson C., Lichtenheld M., Eisen H. N., Podack E. R. Perforin mRNA in primary peritoneal exudate cytotoxic T lymphocytes. J Immunol. 1989 Dec 1;143(11):3440–3443. [PubMed] [Google Scholar]
  17. Nagler-Anderson C., Verret C. R., Firmenich A. A., Berne M., Eisen H. N. Resistance of primary CD8+ cytotoxic T lymphocytes to lysis by cytotoxic granules from cloned T cell lines. J Immunol. 1988 Nov 15;141(10):3299–3305. [PubMed] [Google Scholar]
  18. Ostergaard H. L., Clark W. R. Evidence for multiple lytic pathways used by cytotoxic T lymphocytes. J Immunol. 1989 Oct 1;143(7):2120–2126. [PubMed] [Google Scholar]
  19. Ottenhoff T. H., Mutis T. Specific killing of cytotoxic T cells and antigen-presenting cells by CD4+ cytotoxic T cell clones. A novel potentially immunoregulatory T-T cell interaction in man. J Exp Med. 1990 Jun 1;171(6):2011–2024. doi: 10.1084/jem.171.6.2011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Pasternack M. S., Eisen H. N. A novel serine esterase expressed by cytotoxic T lymphocytes. 1985 Apr 25-May 1Nature. 314(6013):743–745. doi: 10.1038/314743a0. [DOI] [PubMed] [Google Scholar]
  21. Pemberton R. M., Wraith D. C., Askonas B. A. Influenza peptide-induced self-lysis and down-regulation of cloned cytotoxic T cells. Immunology. 1990 Jun;70(2):223–229. [PMC free article] [PubMed] [Google Scholar]
  22. Podack E. R., Young J. D., Cohn Z. A. Isolation and biochemical and functional characterization of perforin 1 from cytolytic T-cell granules. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8629–8633. doi: 10.1073/pnas.82.24.8629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Rosenberg S. A., Grimm E. A., McGrogan M., Doyle M., Kawasaki E., Koths K., Mark D. F. Biological activity of recombinant human interleukin-2 produced in Escherichia coli. Science. 1984 Mar 30;223(4643):1412–1414. doi: 10.1126/science.6367046. [DOI] [PubMed] [Google Scholar]
  24. Schick B., Berke G. The lysis of cytotoxic T lymphocytes and their blasts by cytotoxic T lymphocytes. Immunology. 1990 Nov;71(3):428–433. [PMC free article] [PubMed] [Google Scholar]
  25. Sellins K. S., Cohen J. J. Gene induction by gamma-irradiation leads to DNA fragmentation in lymphocytes. J Immunol. 1987 Nov 15;139(10):3199–3206. [PubMed] [Google Scholar]
  26. Shinkai Y., Ishikawa H., Hattori M., Okumura K. Resistance of mouse cytolytic cells to pore-forming protein-mediated cytolysis. Eur J Immunol. 1988 Jan;18(1):29–33. doi: 10.1002/eji.1830180106. [DOI] [PubMed] [Google Scholar]
  27. Skinner M., Marbrook J. The most efficient cytotoxic T lymphocytes are the least susceptible to lysis. J Immunol. 1987 Aug 15;139(4):985–987. [PubMed] [Google Scholar]
  28. Tirosh R., Berke G. T-Lymphocyte-mediated cytolysis as an excitatory process of the target. I. Evidence that the target cell may be the site of Ca2+ action. Cell Immunol. 1985 Oct 1;95(1):113–123. doi: 10.1016/0008-8749(85)90300-4. [DOI] [PubMed] [Google Scholar]
  29. Verret C. R., Firmenich A. A., Kranz D. M., Eisen H. N. Resistance of cytotoxic T lymphocytes to the lytic effects of their toxic granules. J Exp Med. 1987 Nov 1;166(5):1536–1547. doi: 10.1084/jem.166.5.1536. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Walden P. R., Eisen H. N. Cognate peptides induce self-destruction of CD8+ cytolytic T lymphocytes. Proc Natl Acad Sci U S A. 1990 Nov;87(22):9015–9019. doi: 10.1073/pnas.87.22.9015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Wang A., Lu S. D., Mark D. F. Site-specific mutagenesis of the human interleukin-2 gene: structure-function analysis of the cysteine residues. Science. 1984 Jun 29;224(4656):1431–1433. doi: 10.1126/science.6427925. [DOI] [PubMed] [Google Scholar]
  32. Young J. D., Liu C. C. Multiple mechanisms of lymphocyte-mediated killing. Immunol Today. 1988 May;9(5):140–144. doi: 10.1016/0167-5699(88)91201-7. [DOI] [PubMed] [Google Scholar]

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