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. 1989 Dec;84(6):1701–1706. doi: 10.1172/JCI114352

Regulation of interleukin 3 gene induction in normal human T cells.

S C Guba 1, G Stella 1, L A Turka 1, C H June 1, C B Thompson 1, S G Emerson 1
PMCID: PMC304045  PMID: 2556442

Abstract

The regulation of IL-3 gene induction in human peripheral blood T cells was studied. IL-3 gene expression was inducible by crosslinking of the T cell receptor/CD3 complex using anti-CD3 MAb G19-4. Anti-CD3-induced IL-3 gene expression was found to be limited to the CD28+ T cell subset and could be augmented by costimulating T lymphocytes with antibodies directed against CD28. IL-3 expression could also be induced by costimulation of T cells with both phorbol ester and ionomycin, which are thought to mimic the intracellular effects of T cell receptor-antigen interaction. However, unlike other lymphokines such as IL-2 or granulocyte-macrophage colony-stimulating factor, IL-3 gene expression is not induced by stimulation of cells with phorbol myristate acetate and anti-CD28. We conclude that IL-3 gene regulation is under stringent control since IL-3 gene expression occurs only in the CD28+ subset of T cells, and since IL-3 induction obligately requires increased intracellular calcium.

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Selected References

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

  1. Bot F. J., Dorssers L., Wagemaker G., Löwenberg B. Stimulating spectrum of human recombinant multi-CSF (IL-3) on human marrow precursors: importance of accessory cells. Blood. 1988 Jun;71(6):1609–1614. [PubMed] [Google Scholar]
  2. Broudy V. C., Kaushansky K., Segal G. M., Harlan J. M., Adamson J. W. Tumor necrosis factor type alpha stimulates human endothelial cells to produce granulocyte/macrophage colony-stimulating factor. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7467–7471. doi: 10.1073/pnas.83.19.7467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chatila T., Wong R., Young M., Miller R., Terhorst C., Geha R. S. An immunodeficiency characterized by defective signal transduction in T lymphocytes. N Engl J Med. 1989 Mar 16;320(11):696–702. doi: 10.1056/NEJM198903163201104. [DOI] [PubMed] [Google Scholar]
  4. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  5. Clark S. C., Kamen R. The human hematopoietic colony-stimulating factors. Science. 1987 Jun 5;236(4806):1229–1237. doi: 10.1126/science.3296190. [DOI] [PubMed] [Google Scholar]
  6. Davis L., Vida R., Lipsky P. E. Regulation of human T lymphocyte mitogenesis by antibodies to CD3. J Immunol. 1986 Dec 15;137(12):3758–3767. [PubMed] [Google Scholar]
  7. Emerson S. G., Yang Y. C., Clark S. C., Long M. W. Human recombinant granulocyte-macrophage colony stimulating factor and interleukin 3 have overlapping but distinct hematopoietic activities. J Clin Invest. 1988 Oct;82(4):1282–1287. doi: 10.1172/JCI113727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. June C. H., Ledbetter J. A., Gillespie M. M., Lindsten T., Thompson C. B. T-cell proliferation involving the CD28 pathway is associated with cyclosporine-resistant interleukin 2 gene expression. Mol Cell Biol. 1987 Dec;7(12):4472–4481. doi: 10.1128/mcb.7.12.4472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kelso A., Owens T. Production of two hemopoietic growth factors is differentially regulated in single T lymphocytes activated with an anti-T cell receptor antibody. J Immunol. 1988 Feb 15;140(4):1159–1167. [PubMed] [Google Scholar]
  10. Ledbetter J. A., Martin P. J., Spooner C. E., Wofsy D., Tsu T. T., Beatty P. G., Gladstone P. Antibodies to Tp67 and Tp44 augment and sustain proliferative responses of activated T cells. J Immunol. 1985 Oct;135(4):2331–2336. [PubMed] [Google Scholar]
  11. Ledbetter J. A., Parsons M., Martin P. J., Hansen J. A., Rabinovitch P. S., June C. H. Antibody binding to CD5 (Tp67) and Tp44 T cell surface molecules: effects on cyclic nucleotides, cytoplasmic free calcium, and cAMP-mediated suppression. J Immunol. 1986 Nov 15;137(10):3299–3305. [PubMed] [Google Scholar]
  12. Lindsten T., June C. H., Thompson C. B., Leiden J. M. Regulation of 4F2 heavy-chain gene expression during normal human T-cell activation can be mediated by multiple distinct molecular mechanisms. Mol Cell Biol. 1988 Sep;8(9):3820–3826. doi: 10.1128/mcb.8.9.3820. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Nathan D. G., Sieff C. A. The biological activities and uses of recombinant granulocyte-macrophage and multi-colony stimulating factors. Prog Hematol. 1987;15:1–18. [PubMed] [Google Scholar]
  14. Niemeyer C. M., Sieff C. A., Mathey-Prevot B., Wimperis J. Z., Bierer B. E., Clark S. C., Nathan D. G. Expression of human interleukin-3 (multi-CSF) is restricted to human lymphocytes and T-cell tumor lines. Blood. 1989 Mar;73(4):945–951. [PubMed] [Google Scholar]
  15. Nishizuka Y. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature. 1984 Apr 19;308(5961):693–698. doi: 10.1038/308693a0. [DOI] [PubMed] [Google Scholar]
  16. Oettgen H. C., Terhorst C. The T-cell receptor-T3 complex and T-lymphocyte activation. Hum Immunol. 1987 Mar;18(3):187–204. doi: 10.1016/0198-8859(87)90084-x. [DOI] [PubMed] [Google Scholar]
  17. Sieff C. A., Tsai S., Faller D. V. Interleukin 1 induces cultured human endothelial cell production of granulocyte-macrophage colony-stimulating factor. J Clin Invest. 1987 Jan;79(1):48–51. doi: 10.1172/JCI112806. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Sonoda Y., Yang Y. C., Wong G. G., Clark S. C., Ogawa M. Analysis in serum-free culture of the targets of recombinant human hemopoietic growth factors: interleukin 3 and granulocyte/macrophage-colony-stimulating factor are specific for early developmental stages. Proc Natl Acad Sci U S A. 1988 Jun;85(12):4360–4364. doi: 10.1073/pnas.85.12.4360. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Sood A. K., Pereira D., Weissman S. M. Isolation and partial nucleotide sequence of a cDNA clone for human histocompatibility antigen HLA-B by use of an oligodeoxynucleotide primer. Proc Natl Acad Sci U S A. 1981 Jan;78(1):616–620. doi: 10.1073/pnas.78.1.616. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Thompson C. B., Challoner P. B., Neiman P. E., Groudine M. Expression of the c-myb proto-oncogene during cellular proliferation. 1986 Jan 30-Feb 5Nature. 319(6052):374–380. doi: 10.1038/319374a0. [DOI] [PubMed] [Google Scholar]
  21. Thompson C. B., Lindsten T., Ledbetter J. A., Kunkel S. L., Young H. A., Emerson S. G., Leiden J. M., June C. H. CD28 activation pathway regulates the production of multiple T-cell-derived lymphokines/cytokines. Proc Natl Acad Sci U S A. 1989 Feb;86(4):1333–1337. doi: 10.1073/pnas.86.4.1333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. Weiss A., Imboden J., Hardy K., Stobo J. The role of the antigen receptor/T3 complex in T-cell activation. Adv Exp Med Biol. 1987;213:45–49. doi: 10.1007/978-1-4684-5323-2_5. [DOI] [PubMed] [Google Scholar]
  24. Weiss A., Imboden J., Wiskocil R., Stobo J. The role of T3 in the activation of human T cells. J Clin Immunol. 1984 May;4(3):165–173. doi: 10.1007/BF00914963. [DOI] [PubMed] [Google Scholar]
  25. Wong G. G., Witek J. S., Temple P. A., Wilkens K. M., Leary A. C., Luxenberg D. P., Jones S. S., Brown E. L., Kay R. M., Orr E. C. Human GM-CSF: molecular cloning of the complementary DNA and purification of the natural and recombinant proteins. Science. 1985 May 17;228(4701):810–815. doi: 10.1126/science.3923623. [DOI] [PubMed] [Google Scholar]
  26. Yang Y. C., Ciarletta A. B., Temple P. A., Chung M. P., Kovacic S., Witek-Giannotti J. S., Leary A. C., Kriz R., Donahue R. E., Wong G. G. Human IL-3 (multi-CSF): identification by expression cloning of a novel hematopoietic growth factor related to murine IL-3. Cell. 1986 Oct 10;47(1):3–10. doi: 10.1016/0092-8674(86)90360-0. [DOI] [PubMed] [Google Scholar]

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