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Immunology logoLink to Immunology
. 1994 Jan;81(1):21–26.

Dexamethasone induces apoptosis in mouse natural killer cells and cytotoxic T lymphocytes.

G Migliorati 1, I Nicoletti 1, F D'Adamio 1, A Spreca 1, C Pagliacci 1, C Riccardi 1
PMCID: PMC1422297  PMID: 8132215

Abstract

Glucocorticoid hormones (GCH) induce apoptotic cell death in immature thymocytes through an active mechanism, characterized by extensive DNA fragmentation into oligonucleosomal subunits. This requires macromolecular synthesis and is inhibited by protein kinase C (PKC) inhibitors, interleukin-4 (IL-4) and heat shock (hs). We performed experiments to analyse the possible effect of GCH on more differentiated lymphocytes, i.e. mouse natural killer (NK) cells and CD8+ alloreactive cytotoxic T lymphocytes (CTL). The results show that dexamethasone (DEX) induces DNA fragmentation and cell death in NK cells and CTL in vitro. In both NK cells and CTL, DEX-induced apoptosis is inhibited by IL-2 and IL-4 but, unlike that induced in thymocytes, is augmented by mRNA and protein synthesis inhibitors, PKC inhibitors and HS.

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Selected References

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  1. Arends M. J., Morris R. G., Wyllie A. H. Apoptosis. The role of the endonuclease. Am J Pathol. 1990 Mar;136(3):593–608. [PMC free article] [PubMed] [Google Scholar]
  2. Bursch W., Oberhammer F., Schulte-Hermann R. Cell death by apoptosis and its protective role against disease. Trends Pharmacol Sci. 1992 Jun;13(6):245–251. doi: 10.1016/0165-6147(92)90077-j. [DOI] [PubMed] [Google Scholar]
  3. Carlow D. A., Teh S. J., van Oers N. S., Miller R. G., Teh H. S. Peripheral tolerance through clonal deletion of mature CD4-CD8+ T cells. Int Immunol. 1992 May;4(5):599–610. doi: 10.1093/intimm/4.5.599. [DOI] [PubMed] [Google Scholar]
  4. Cohen J. J. Apoptosis. Immunol Today. 1993 Mar;14(3):126–130. doi: 10.1016/0167-5699(93)90214-6. [DOI] [PubMed] [Google Scholar]
  5. Cohen J. J., Duke R. C. Glucocorticoid activation of a calcium-dependent endonuclease in thymocyte nuclei leads to cell death. J Immunol. 1984 Jan;132(1):38–42. [PubMed] [Google Scholar]
  6. Dent A. L., Matis L. A., Hooshmand F., Widacki S. M., Bluestone J. A., Hedrick S. M. Self-reactive gamma delta T cells are eliminated in the thymus. Nature. 1990 Feb 22;343(6260):714–719. doi: 10.1038/343714a0. [DOI] [PubMed] [Google Scholar]
  7. Jenkinson E. J., Kingston R., Smith C. A., Williams G. T., Owen J. J. Antigen-induced apoptosis in developing T cells: a mechanism for negative selection of the T cell receptor repertoire. Eur J Immunol. 1989 Nov;19(11):2175–2177. doi: 10.1002/eji.1830191132. [DOI] [PubMed] [Google Scholar]
  8. Kerr J. F., Wyllie A. H., Currie A. R. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972 Aug;26(4):239–257. doi: 10.1038/bjc.1972.33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. MacDonald H. R., Lees R. K. Programmed death of autoreactive thymocytes. Nature. 1990 Feb 15;343(6259):642–644. doi: 10.1038/343642a0. [DOI] [PubMed] [Google Scholar]
  10. McConkey D. J., Hartzell P., Amador-Pérez J. F., Orrenius S., Jondal M. Calcium-dependent killing of immature thymocytes by stimulation via the CD3/T cell receptor complex. J Immunol. 1989 Sep 15;143(6):1801–1806. [PubMed] [Google Scholar]
  11. McConkey D. J., Hartzell P., Chow S. C., Orrenius S., Jondal M. Interleukin 1 inhibits T cell receptor-mediated apoptosis in immature thymocytes. J Biol Chem. 1990 Feb 25;265(6):3009–3011. [PubMed] [Google Scholar]
  12. Migliorati G., Moraca R., Nicoletti I., Riccardi C. IL-2-dependent generation of natural killer cells from bone marrow: role of MAC-1-, NK1-1- precursors. Cell Immunol. 1992 May;141(2):323–331. doi: 10.1016/0008-8749(92)90151-e. [DOI] [PubMed] [Google Scholar]
  13. Migliorati G., Nicoletti I., Crocicchio F., Pagliacci C., D'Adamio F., Riccardi C. Heat shock induces apoptosis in mouse thymocytes and protects them from glucocorticoid-induced cell death. Cell Immunol. 1992 Sep;143(2):348–356. doi: 10.1016/0008-8749(92)90031-j. [DOI] [PubMed] [Google Scholar]
  14. Migliorati G., Pagliacci C., Moraca R., Crocicchio F., Nicoletti I., Riccardi C. Interleukins modulate glucocorticoid-induced thymocyte apoptosis. Int J Clin Lab Res. 1992;21(4):300–303. doi: 10.1007/BF02591666. [DOI] [PubMed] [Google Scholar]
  15. Nicoletti I., Migliorati G., Pagliacci M. C., Grignani F., Riccardi C. A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry. J Immunol Methods. 1991 Jun 3;139(2):271–279. doi: 10.1016/0022-1759(91)90198-o. [DOI] [PubMed] [Google Scholar]
  16. Nieto M. A., González A., López-Rivas A., Diaz-Espada F., Gambón F. IL-2 protects against anti-CD3-induced cell death in human medullary thymocytes. J Immunol. 1990 Sep 1;145(5):1364–1368. [PubMed] [Google Scholar]
  17. Nieto M. A., López-Rivas A. IL-2 protects T lymphocytes from glucocorticoid-induced DNA fragmentation and cell death. J Immunol. 1989 Dec 15;143(12):4166–4170. [PubMed] [Google Scholar]
  18. Rocha B., von Boehmer H. Peripheral selection of the T cell repertoire. Science. 1991 Mar 8;251(4998):1225–1228. doi: 10.1126/science.1900951. [DOI] [PubMed] [Google Scholar]
  19. Searle J., Lawson T. A., Abbott P. J., Harmon B., Kerr J. F. An electron-microscope study of the mode of cell death induced by cancer-chemotherapeutic agents in populations of proliferating normal and neoplastic cells. J Pathol. 1975 Jul;116(3):129–138. doi: 10.1002/path.1711160302. [DOI] [PubMed] [Google Scholar]
  20. Shenoy A. M., Brahmi Z. Inhibition of the calpain-mediated proteolysis of protein kinase C enhances lytic activity in human NK cells. Cell Immunol. 1991 Nov;138(1):24–34. doi: 10.1016/0008-8749(91)90129-y. [DOI] [PubMed] [Google Scholar]
  21. Smith C. A., Williams G. T., Kingston R., Jenkinson E. J., Owen J. J. Antibodies to CD3/T-cell receptor complex induce death by apoptosis in immature T cells in thymic cultures. Nature. 1989 Jan 12;337(6203):181–184. doi: 10.1038/337181a0. [DOI] [PubMed] [Google Scholar]
  22. Trinchieri G. Biology of natural killer cells. Adv Immunol. 1989;47:187–376. doi: 10.1016/S0065-2776(08)60664-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Umansky S. R., Korol' B. A., Nelipovich P. A. In vivo DNA degradation in thymocytes of gamma-irradiated or hydrocortisone-treated rats. Biochim Biophys Acta. 1981 Aug 27;655(1):9–17. doi: 10.1016/0005-2787(81)90060-5. [DOI] [PubMed] [Google Scholar]
  24. Wyllie A. H. Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature. 1980 Apr 10;284(5756):555–556. doi: 10.1038/284555a0. [DOI] [PubMed] [Google Scholar]
  25. Wyllie A. H., Kerr J. F., Currie A. R. Cell death: the significance of apoptosis. Int Rev Cytol. 1980;68:251–306. doi: 10.1016/s0074-7696(08)62312-8. [DOI] [PubMed] [Google Scholar]
  26. Zacharchuk C. M., Merćep M., Chakraborti P. K., Simons S. S., Jr, Ashwell J. D. Programmed T lymphocyte death. Cell activation- and steroid-induced pathways are mutually antagonistic. J Immunol. 1990 Dec 15;145(12):4037–4045. [PubMed] [Google Scholar]

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