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. 1989 Apr;66(4):539–545.

Interactive effects of pertussis toxin and the phorbol ester tumour promotor, phorbol dibutyrate, on T-lymphocyte mitogenesis and the expression of phenotypic determinants.

C F Strnad 1, W Q Lin 1, R A Carchman 1
PMCID: PMC1385154  PMID: 2469642

Abstract

The B oligomer of pertussis toxin serves as a weak mitogen in the T lymphocyte, an effect which is associated with an early rise in cytosolic free calcium concentrations, as monitored by Fura-2 fluorescence. Upon co-administration of phorbol dibutyrate, a phorbol ester tumour promotor which activates protein kinase C, pertussis toxin-induced proliferation was synergistically enhanced, as measured by the increased uptake of [3H]thymidine, into cellular DNA. Although phorbol ester co-administration has often been associated with an inhibition of Ca2+-mobilizing pathways, phorbol dibutyrate pretreatment had no inhibitory effect on the pertussis toxin-induced calcium flux and may actually have enhanced this response slightly. Flow cytometric analysis of cell populations expanded by the combined regimen did not provide evidence for the preferential expansion of cells bearing either CD4 or CD8, the T-cell determinants representative of the helper-inducer and cytotoxic-suppressor subsets, respectively. Pertussis toxin and phorbol dibutyrate appear, therefore, to elicit polyclonal stimulation, rather than the selective activation of a given lymphocyte subset. Expression of the transferrin receptor, a marker for nutrient uptake, and CD25, the Tac component of the interleukin-2 (IL-2) receptor, was, however, synergistically enhanced in cells activated by the co-treatment procedure.

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Selected References

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

  1. Arciniega J. L., Burns D. L., Garcia-Ortigoza E., Manclark C. R. Immune response to the B oligomer of pertussis toxin. Infect Immun. 1987 May;55(5):1132–1136. doi: 10.1128/iai.55.5.1132-1136.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Berridge M. J., Irvine R. F. Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature. 1984 Nov 22;312(5992):315–321. doi: 10.1038/312315a0. [DOI] [PubMed] [Google Scholar]
  3. Bomford A., Young S. P., Nouri-Aria K., Williams R. Uptake and release of transferrin and iron by mitogen-stimulated human lymphocytes. Br J Haematol. 1983 Sep;55(1):93–101. doi: 10.1111/j.1365-2141.1983.tb01227.x. [DOI] [PubMed] [Google Scholar]
  4. Brock J. H., Mainou-Fowler T., Webster L. M. Evidence that transferrin may function exclusively as an iron donor in promoting lymphocyte proliferation. Immunology. 1986 Jan;57(1):105–110. [PMC free article] [PubMed] [Google Scholar]
  5. Burns D. L., Manclark C. R. Adenine nucleotides promote dissociation of pertussis toxin subunits. J Biol Chem. 1986 Mar 25;261(9):4324–4327. [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. Dixon S. J., Stewart D., Grinstein S., Spiegel S. Transmembrane signaling by the B subunit of cholera toxin: increased cytoplasmic free calcium in rat lymphocytes. J Cell Biol. 1987 Sep;105(3):1153–1161. doi: 10.1083/jcb.105.3.1153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Grewal I. S., Olson C. V., Scott S. J., Lad P. M. Cap formation in a B-lymphocyte cell line is inhibited by pertussis toxin and phorbol ester. Immunology. 1987 Jun;61(2):131–135. [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. Hara T., Fu S. M. Human T cell activation. I. Monocyte-independent activation and proliferation induced by anti-T3 monoclonal antibodies in the presence of tumor promoter 12-o-tetradecanoyl phorbol-13 acetate. J Exp Med. 1985 Apr 1;161(4):641–656. doi: 10.1084/jem.161.4.641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ho M. K., Kong A. S., Morse S. I. The in vitro effects of Bordetella pertussis lymphocytosis-promoting factor on murine lymphocytes. III. B-cell dependence for T-cell proliferation. J Exp Med. 1979 May 1;149(5):1001–1017. doi: 10.1084/jem.149.5.1001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hoxie J. A., Matthews D. M., Callahan K. J., Cassel D. L., Cooper R. A. Transient modulation and internalization of T4 antigen induced by phorbol esters. J Immunol. 1986 Aug 15;137(4):1194–1201. [PubMed] [Google Scholar]
  13. Imboden J. B., Stobo J. D. Transmembrane signalling by the T cell antigen receptor. Perturbation of the T3-antigen receptor complex generates inositol phosphates and releases calcium ions from intracellular stores. J Exp Med. 1985 Mar 1;161(3):446–456. doi: 10.1084/jem.161.3.446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kong A. S., Morse S. I. The in vitro effects of Bordetella pertussis lymphocytosis-promoting factor on murine lymphocytes: II. Nature of the responding cells. J Exp Med. 1977 Jan 1;145(1):163–174. doi: 10.1084/jem.145.1.163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. LAGERGREN J. The white blood cell count and the erythrocyte sedimentation rate in pertussis. Acta Paediatr. 1963 Jul;52:405–409. doi: 10.1111/j.1651-2227.1963.tb03798.x. [DOI] [PubMed] [Google Scholar]
  16. Lad P. M., Olson C. V., Smiley P. A. Association of the N-formyl-Met-Leu-Phe receptor in human neutrophils with a GTP-binding protein sensitive to pertussis toxin. Proc Natl Acad Sci U S A. 1985 Feb;82(3):869–873. doi: 10.1073/pnas.82.3.869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Macintyre E. A., Tatham P. E., Abdul-Gaffar R., Linch D. C. The effects of pertussis toxin on human T lymphocytes. Immunology. 1988 Jul;64(3):427–432. [PMC free article] [PubMed] [Google Scholar]
  18. Miller D. L., Ross E. M., Alderslade R., Bellman M. H., Rawson N. S. Pertussis immunisation and serious acute neurological illness in children. Br Med J (Clin Res Ed) 1981 May 16;282(6276):1595–1599. doi: 10.1136/bmj.282.6276.1595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Moreno F. J., Mills I., García-Sáinz J. A., Fain J. N. Effects of pertussis toxin treatment on the metabolism of rat adipocytes. J Biol Chem. 1983 Sep 25;258(18):10938–10943. [PubMed] [Google Scholar]
  20. Morse S. I., Bray K. K. The occurrence and properties of leukocytosis and lymphocytosis-stimulating material in the supernatant fluids of Bordetella pertussis cultures. J Exp Med. 1969 Mar 1;129(3):523–550. doi: 10.1084/jem.129.3.523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Morse S. I., Morse J. H. Isolation and properties of the leukocytosis- and lymphocytosis-promoting factor of Bordetella pertussis. J Exp Med. 1976 Jun 1;143(6):1483–1502. doi: 10.1084/jem.143.6.1483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Murayama T., Ui M. Loss of the inhibitory function of the guanine nucleotide regulatory component of adenylate cyclase due to its ADP ribosylation by islet-activating protein, pertussis toxin, in adipocyte membranes. J Biol Chem. 1983 Mar 10;258(5):3319–3326. [PubMed] [Google Scholar]
  23. Nakamura T., Ui M. Suppression of passive cutaneous anaphylaxis by pertussis toxin, an islet-activating protein, as a result of inhibition of histamine release from mast cells. Biochem Pharmacol. 1983 Nov 15;32(22):3435–3441. doi: 10.1016/0006-2952(83)90373-8. [DOI] [PubMed] [Google Scholar]
  24. Okajima F., Katada T., Ui M. Coupling of the guanine nucleotide regulatory protein to chemotactic peptide receptors in neutrophil membranes and its uncoupling by islet-activating protein, pertussis toxin. A possible role of the toxin substrate in Ca2+-mobilizing receptor-mediated signal transduction. J Biol Chem. 1985 Jun 10;260(11):6761–6768. [PubMed] [Google Scholar]
  25. Rosoff P. M., Walker R., Winberry L. Pertussis toxin triggers rapid second messenger production in human T lymphocytes. J Immunol. 1987 Oct 1;139(7):2419–2423. [PubMed] [Google Scholar]
  26. Steinman L., Weiss A., Adelman N., Lim M., Zuniga R., Oehlert J., Hewlett E., Falkow S. Pertussis toxin is required for pertussis vaccine encephalopathy. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8733–8736. doi: 10.1073/pnas.82.24.8733. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Strnad C. F., Carchman R. A. Human T lymphocyte mitogenesis in response to the B oligomer of pertussis toxin is associated with an early elevation in cytosolic calcium concentrations. FEBS Lett. 1987 Dec 10;225(1-2):16–20. doi: 10.1016/0014-5793(87)81123-7. [DOI] [PubMed] [Google Scholar]
  28. Tamura M., Nogimori K., Murai S., Yajima M., Ito K., Katada T., Ui M., Ishii S. Subunit structure of islet-activating protein, pertussis toxin, in conformity with the A-B model. Biochemistry. 1982 Oct 26;21(22):5516–5522. doi: 10.1021/bi00265a021. [DOI] [PubMed] [Google Scholar]
  29. Tamura M., Nogimori K., Yajima M., Ase K., Ui M. A role of the B-oligomer moiety of islet-activating protein, pertussis toxin, in development of the biological effects on intact cells. J Biol Chem. 1983 Jun 10;258(11):6756–6761. [PubMed] [Google Scholar]
  30. Truneh A., Albert F., Golstein P., Schmitt-Verhulst A. M. Early steps of lymphocyte activation bypassed by synergy between calcium ionophores and phorbol ester. Nature. 1985 Jan 24;313(6000):318–320. doi: 10.1038/313318a0. [DOI] [PubMed] [Google Scholar]
  31. Vistica B. P., McAllister C. G., Sekura R. D., Ihle J. N., Gery I. Dual effects of pertussis toxin on lymphoid cells in culture. Cell Immunol. 1986 Aug;101(1):232–241. doi: 10.1016/0008-8749(86)90200-5. [DOI] [PubMed] [Google Scholar]
  32. Yajima M., Hosoda K., Kanbayashi Y., Nakamura T., Nogimori K., Mizushima Y., Nakase Y., Ui M. Islets-activating protein (IAP) in Bordetella pertussis that potentiates insulin secretory responses of rats. Purification and characterization. J Biochem. 1978 Jan;83(1):295–303. doi: 10.1093/oxfordjournals.jbchem.a131904. [DOI] [PubMed] [Google Scholar]

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