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. 1998 Mar;93(3):383–389. doi: 10.1046/j.1365-2567.1998.00448.x

The CD8+ granzyme B+ T-cell subset in peripheral blood from healthy individuals contains activated and apoptosis-prone cells.

P C Wever 1, H J Van Der Vliet 1, L H Spaeny 1, A M Wolbink 1, F N Van Diepen 1, C J Froelich 1, C E Hack 1, I J ten Berge 1
PMCID: PMC1364087  PMID: 9640249

Abstract

Granzyme B (GrB) has been implicated in induction of apoptosis in target cells. The presence of GrB in peripheral blood CD8+ T cells from healthy individuals was analysed in immunocytochemical and flow cytometric studies. Furthermore, CD8+ GrB- T cells and CD8+ GrB+ T cells were compared regarding phenotypical characteristics and susceptibility to both spontaneous and Fasmediated apoptosis. GrB was expressed by approximately one-fifth of CD8+ T cells. Compared with the CD8+ GrB- T-cell subset, the CD8+ GrB+ T-cell subset contained cells that were relatively more activated and more prone to spontaneous apoptosis. Culturing of cells with immunoglobulin M (IgM) anti-Fas monoclonal antibody had no additional effect on the number of CD8+ GrB+ T cells undergoing apoptosis. We suggest that the presence of CD8+ GrB+ T cells in peripheral blood from healthy individuals results from immune surveillance or contact with infectious agents, and that spontaneous apoptosis of these cells might serve as a mechanism for their eventual clearance.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akbar A. N., Borthwick N., Salmon M., Gombert W., Bofill M., Shamsadeen N., Pilling D., Pett S., Grundy J. E., Janossy G. The significance of low bcl-2 expression by CD45RO T cells in normal individuals and patients with acute viral infections. The role of apoptosis in T cell memory. J Exp Med. 1993 Aug 1;178(2):427–438. doi: 10.1084/jem.178.2.427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alnemri E. S., Livingston D. J., Nicholson D. W., Salvesen G., Thornberry N. A., Wong W. W., Yuan J. Human ICE/CED-3 protease nomenclature. Cell. 1996 Oct 18;87(2):171–171. doi: 10.1016/s0092-8674(00)81334-3. [DOI] [PubMed] [Google Scholar]
  3. Azuma M., Cayabyab M., Phillips J. H., Lanier L. L. Requirements for CD28-dependent T cell-mediated cytotoxicity. J Immunol. 1993 Mar 15;150(6):2091–2101. [PubMed] [Google Scholar]
  4. Azuma M., Phillips J. H., Lanier L. L. CD28- T lymphocytes. Antigenic and functional properties. J Immunol. 1993 Feb 15;150(4):1147–1159. [PubMed] [Google Scholar]
  5. Berthou C., Legros-Maïda S., Soulié A., Wargnier A., Guillet J., Rabian C., Gluckman E., Sasportes M. Cord blood T lymphocytes lack constitutive perforin expression in contrast to adult peripheral blood T lymphocytes. Blood. 1995 Mar 15;85(6):1540–1546. [PubMed] [Google Scholar]
  6. Boudet F., Lecoeur H., Gougeon M. L. Apoptosis associated with ex vivo down-regulation of Bcl-2 and up-regulation of Fas in potential cytotoxic CD8+ T lymphocytes during HIV infection. J Immunol. 1996 Mar 15;156(6):2282–2293. [PubMed] [Google Scholar]
  7. Chinnaiyan A. M., Dixit V. M. The cell-death machine. Curr Biol. 1996 May 1;6(5):555–562. doi: 10.1016/s0960-9822(02)00541-9. [DOI] [PubMed] [Google Scholar]
  8. Cohen J. J. Apoptosis. Immunol Today. 1993 Mar;14(3):126–130. doi: 10.1016/0167-5699(93)90214-6. [DOI] [PubMed] [Google Scholar]
  9. Ebnet K., Hausmann M., Lehmann-Grube F., Müllbacher A., Kopf M., Lamers M., Simon M. M. Granzyme A-deficient mice retain potent cell-mediated cytotoxicity. EMBO J. 1995 Sep 1;14(17):4230–4239. doi: 10.1002/j.1460-2075.1995.tb00097.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Emlen W., Niebur J., Kadera R. Accelerated in vitro apoptosis of lymphocytes from patients with systemic lupus erythematosus. J Immunol. 1994 Apr 1;152(7):3685–3692. [PubMed] [Google Scholar]
  11. Hack C. E., Paardekooper J., Smeenk R. J., Abbink J., Eerenberg A. J., Nuijens J. H. Disruption of the internal thioester bond in the third component of complement (C3) results in the exposure of neodeterminants also present on activation products of C3. An analysis with monoclonal antibodies. J Immunol. 1988 Sep 1;141(5):1602–1609. [PubMed] [Google Scholar]
  12. Hanna W. L., Zhang X., Turbov J., Winkler U., Hudig D., Froelich C. J. Rapid purification of cationic granule proteases: application to human granzymes. Protein Expr Purif. 1993 Oct;4(5):398–404. doi: 10.1006/prep.1993.1052. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Heusel J. W., Wesselschmidt R. L., Shresta S., Russell J. H., Ley T. J. Cytotoxic lymphocytes require granzyme B for the rapid induction of DNA fragmentation and apoptosis in allogeneic target cells. Cell. 1994 Mar 25;76(6):977–987. doi: 10.1016/0092-8674(94)90376-x. [DOI] [PubMed] [Google Scholar]
  15. Ju S. T., Panka D. J., Cui H., Ettinger R., el-Khatib M., Sherr D. H., Stanger B. Z., Marshak-Rothstein A. Fas(CD95)/FasL interactions required for programmed cell death after T-cell activation. Nature. 1995 Feb 2;373(6513):444–448. doi: 10.1038/373444a0. [DOI] [PubMed] [Google Scholar]
  16. Koizumi H., Liu C. C., Zheng L. M., Joag S. V., Bayne N. K., Holoshitz J., Young J. D. Expression of perforin and serine esterases by human gamma/delta T cells. J Exp Med. 1991 Feb 1;173(2):499–502. doi: 10.1084/jem.173.2.499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Koopman G., Reutelingsperger C. P., Kuijten G. A., Keehnen R. M., Pals S. T., van Oers M. H. Annexin V for flow cytometric detection of phosphatidylserine expression on B cells undergoing apoptosis. Blood. 1994 Sep 1;84(5):1415–1420. [PubMed] [Google Scholar]
  18. Kummer J. A., Kamp A. M., Tadema T. M., Vos W., Meijer C. J., Hack C. E. Localization and identification of granzymes A and B-expressing cells in normal human lymphoid tissue and peripheral blood. Clin Exp Immunol. 1995 Apr;100(1):164–172. doi: 10.1111/j.1365-2249.1995.tb03619.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lebow L. T., Bonavida B. Purification and characterization of cytolytic and noncytolytic human natural killer cell subsets. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6063–6067. doi: 10.1073/pnas.87.16.6063. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Liu C. C., Rafii S., Granelli-Piperno A., Trapani J. A., Young J. D. Perforin and serine esterase gene expression in stimulated human T cells. Kinetics, mitogen requirements, and effects of cyclosporin A. J Exp Med. 1989 Dec 1;170(6):2105–2118. doi: 10.1084/jem.170.6.2105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Liu C. C., Walsh C. M., Young J. D. Perforin: structure and function. Immunol Today. 1995 Apr;16(4):194–201. doi: 10.1016/0167-5699(95)80121-9. [DOI] [PubMed] [Google Scholar]
  22. Martin S. J., Reutelingsperger C. P., McGahon A. J., Rader J. A., van Schie R. C., LaFace D. M., Green D. R. Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl. J Exp Med. 1995 Nov 1;182(5):1545–1556. doi: 10.1084/jem.182.5.1545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Massaia M., Borrione P., Attisano C., Barral P., Beggiato E., Montacchini L., Bianchi A., Boccadoro M., Pileri A. Dysregulated Fas and Bcl-2 expression leading to enhanced apoptosis in T cells of multiple myeloma patients. Blood. 1995 Jun 15;85(12):3679–3687. [PubMed] [Google Scholar]
  24. Miyawaki T., Uehara T., Nibu R., Tsuji T., Yachie A., Yonehara S., Taniguchi N. Differential expression of apoptosis-related Fas antigen on lymphocyte subpopulations in human peripheral blood. J Immunol. 1992 Dec 1;149(11):3753–3758. [PubMed] [Google Scholar]
  25. Monteiro J., Batliwalla F., Ostrer H., Gregersen P. K. Shortened telomeres in clonally expanded CD28-CD8+ T cells imply a replicative history that is distinct from their CD28+CD8+ counterparts. J Immunol. 1996 May 15;156(10):3587–3590. [PubMed] [Google Scholar]
  26. Owen-Schaub L. B., Yonehara S., Crump W. L., 3rd, Grimm E. A. DNA fragmentation and cell death is selectively triggered in activated human lymphocytes by Fas antigen engagement. Cell Immunol. 1992 Mar;140(1):197–205. doi: 10.1016/0008-8749(92)90187-t. [DOI] [PubMed] [Google Scholar]
  27. Roederer M., Dubs J. G., Anderson M. T., Raju P. A., Herzenberg L. A., Herzenberg L. A. CD8 naive T cell counts decrease progressively in HIV-infected adults. J Clin Invest. 1995 May;95(5):2061–2066. doi: 10.1172/JCI117892. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Salcedo T. W., Azzoni L., Wolf S. F., Perussia B. Modulation of perforin and granzyme messenger RNA expression in human natural killer cells. J Immunol. 1993 Sep 1;151(5):2511–2520. [PubMed] [Google Scholar]
  29. Slaper-Cortenbach I. C., Admiraal L. G., Kerr J. M., van Leeuwen E. F., von dem Borne A. E., Tetteroo P. A. Flow-cytometric detection of terminal deoxynucleotidyl transferase and other intracellular antigens in combination with membrane antigens in acute lymphatic leukemias. Blood. 1988 Nov;72(5):1639–1644. [PubMed] [Google Scholar]
  30. Su B., Bochan M. R., Hanna W. L., Froelich C. J., Brahmi Z. Human granzyme B is essential for DNA fragmentation of susceptible target cells. Eur J Immunol. 1994 Sep;24(9):2073–2080. doi: 10.1002/eji.1830240921. [DOI] [PubMed] [Google Scholar]
  31. Sunder-Plassmann G., Wagner L., Hruby K., Balcke P., Worman C. P. Upregulation of a lymphoid serine protease in kidney allograft recipients. Kidney Int. 1990 May;37(5):1350–1356. doi: 10.1038/ki.1990.121. [DOI] [PubMed] [Google Scholar]
  32. Testi R., D'Ambrosio D., De Maria R., Santoni A. The CD69 receptor: a multipurpose cell-surface trigger for hematopoietic cells. Immunol Today. 1994 Oct;15(10):479–483. doi: 10.1016/0167-5699(94)90193-7. [DOI] [PubMed] [Google Scholar]
  33. Trapani J. A., Klein J. L., White P. C., Dupont B. Molecular cloning of an inducible serine esterase gene from human cytotoxic lymphocytes. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6924–6928. doi: 10.1073/pnas.85.18.6924. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Wever P. C., Mulder J. B., Weening J. J., ten Berge I. J. Immunocytochemical detection of granzymes A and B in peripheral blood lymphocytes from healthy individuals after non-enzymatic antigen retrieval. J Histochem Cytochem. 1997 Mar;45(3):467–469. doi: 10.1177/002215549704500315. [DOI] [PubMed] [Google Scholar]

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