Skip to main content
NCBI home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1992 Jul;89(1):158–163. doi: 10.1111/j.1365-2249.1992.tb06896.x

Intracellular free Ca2+ fluxes and responses to phorbol ester in T lymphocytes from healthy elderly subjects.

J R Naylor 1, S R James 1, L K Trejdosiewicz 1
PMCID: PMC1554407  PMID: 1385766

Abstract

A group of healthy elderly subjects (greater than or equal to 75 years) was selected by the strict criteria of the SENIEUR protocol, and compared with healthy young (less than or equal to 35 years) volunteers. Mitogenic responses of peripheral blood mononuclear cells to phytohaemagglutinin and anti-CD3 were significantly reduced in the elderly (P less than 0.0002), thereby confirming that even though in perfect health, elderly individuals show impaired cell-mediated immunity. However, no abnormality of intracellular free Ca2+ fluxes could be detected in purified T cells from the elderly subjects when stimulated with anti-CD3 antibody. Nevertheless, both the proliferative responses of purified T cells to phorbol ester and calcium ionophore (Ionomycin) and the phorbol ester-induced inhibition of the Ca2+ response were defective in the elderly subjects (P less than 0.003 and P less than 0.0002, respectively). These data suggest that signal transduction and the generation of second messengers proceed normally in T cells from the elderly, but downstream events mediated by activation of protein kinase C are dysfunctional.

Full text

PDF
158

Selected References

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

  1. Berridge M. J., Irvine R. F. Inositol phosphates and cell signalling. Nature. 1989 Sep 21;341(6239):197–205. doi: 10.1038/341197a0. [DOI] [PubMed] [Google Scholar]
  2. Berry N., Ase K., Kikkawa U., Kishimoto A., Nishizuka Y. Human T cell activation by phorbol esters and diacylglycerol analogues. J Immunol. 1989 Sep 1;143(5):1407–1413. [PubMed] [Google Scholar]
  3. Bijsterbosch M. K., Klaus G. G. Tumor-promoting phorbol esters suppress receptor-stimulated inositol phospholipid degradation and Ca2+ mobilization in mouse lymphocytes. Eur J Immunol. 1987 Jan;17(1):113–118. doi: 10.1002/eji.1830170119. [DOI] [PubMed] [Google Scholar]
  4. Blumenthal E. J., Malkinson A. M. Age-dependent changes in murine protein kinase and protease enzymes. Mech Ageing Dev. 1988 Dec;46(1-3):201–217. doi: 10.1016/0047-6374(88)90125-x. [DOI] [PubMed] [Google Scholar]
  5. Callard R. E., Basten A. Immune function in aged mice. IV. Loss of T cell and B cell function in thymus-dependent antibody responses. Eur J Immunol. 1978 Aug;8(8):552–558. doi: 10.1002/eji.1830080803. [DOI] [PubMed] [Google Scholar]
  6. Cantrell D. A., Davies A. A., Crumpton M. J. Activators of protein kinase C down-regulate and phosphorylate the T3/T-cell antigen receptor complex of human T lymphocytes. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8158–8162. doi: 10.1073/pnas.82.23.8158. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cantrell D. A., Lucas S. C., Ward S., Westwick J., Gullberg M. Phorbol esters regulate CD2- and CD3-mediated calcium responses in peripheral blood-derived human T cells. J Immunol. 1989 Dec 1;143(11):3653–3658. [PubMed] [Google Scholar]
  8. Chopra R. K., Holbrook N. J., Powers D. C., McCoy M. T., Adler W. H., Nagel J. E. Interleukin 2, interleukin 2 receptor, and interferon-gamma synthesis and mRNA expression in phorbol myristate acetate and calcium ionophore A23187-stimulated T cells from elderly humans. Clin Immunol Immunopathol. 1989 Nov;53(2 Pt 1):297–308. doi: 10.1016/0090-1229(89)90058-5. [DOI] [PubMed] [Google Scholar]
  9. Chopra R. K., Nagel J. E., Chrest F. J., Adler W. H. Impaired phorbol ester and calcium ionophore induced proliferation of T cells from old humans. Clin Exp Immunol. 1987 Nov;70(2):456–462. [PMC free article] [PubMed] [Google Scholar]
  10. Connolly T. M., Lawing W. J., Jr, Majerus P. W. Protein kinase C phosphorylates human platelet inositol trisphosphate 5'-phosphomonoesterase, increasing the phosphatase activity. Cell. 1986 Sep 12;46(6):951–958. doi: 10.1016/0092-8674(86)90077-2. [DOI] [PubMed] [Google Scholar]
  11. Gamble D. A., Schwab R., Weksler M. E., Szabo P. Decreased steady state c-myc mRNA in activated T cell cultures from old humans is caused by a smaller proportion of T cells that transcribe the c-myc gene. J Immunol. 1990 May 1;144(9):3569–3573. [PubMed] [Google Scholar]
  12. Grynkiewicz G., Poenie M., Tsien R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed] [Google Scholar]
  13. Ligthart G. J., Corberand J. X., Fournier C., Galanaud P., Hijmans W., Kennes B., Müller-Hermelink H. K., Steinmann G. G. Admission criteria for immunogerontological studies in man: the SENIEUR protocol. Mech Ageing Dev. 1984 Nov;28(1):47–55. doi: 10.1016/0047-6374(84)90152-0. [DOI] [PubMed] [Google Scholar]
  14. Ligthart G. J., Schuit H. R., Hijmans W. Subpopulations of mononuclear cells in ageing: expansion of the null cell compartment and decrease in the number of T and B cells in human blood. Immunology. 1985 May;55(1):15–21. [PMC free article] [PubMed] [Google Scholar]
  15. Molecular interactions in aging and cancer. Proceedings of a symposium of the 39th annual scientific meeting of The Gerontological Society of America. J Gerontol. 1989 Nov;44(6):1–80. [PubMed] [Google Scholar]
  16. Nagel J. E., Chopra R. K., Chrest F. J., McCoy M. T., Schneider E. L., Holbrook N. J., Adler W. H. Decreased proliferation, interleukin 2 synthesis, and interleukin 2 receptor expression are accompanied by decreased mRNA expression in phytohemagglutinin-stimulated cells from elderly donors. J Clin Invest. 1988 Apr;81(4):1096–1102. doi: 10.1172/JCI113422. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Nishizuka Y. Studies and perspectives of protein kinase C. Science. 1986 Jul 18;233(4761):305–312. doi: 10.1126/science.3014651. [DOI] [PubMed] [Google Scholar]
  18. Treves S., Di Virgilio F., Cerundolo V., Zanovello P., Collavo D., Pozzan T. Calcium and inositolphosphates in the activation of T cell-mediated cytotoxicity. J Exp Med. 1987 Jul 1;166(1):33–42. doi: 10.1084/jem.166.1.33. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES