Skip to main content
SpringerLink
Log in

Effect of dexamethasone on T-cell receptor/CD3 expression

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Glucocorticoid hormones (GCH) are anti-inflammatory and immunosuppressive agents that inhibit T-cell growth and activation. Since the T-cell receptor (TCR)/CD3 complex mediates T-lymphocyte activation, we studied the effect of in vitro dexamethasone (DEX), a synthetic GCH, on TCR/CD3 expression.

DEX-treatment of a hybridoma T-cell line and normal un-transformed T-cell clones induced a decrease of the TCR/CD3 membrane expression after 4 days. After 4 weeks, TCR/CD3 was undetectable. However, the amount of mRNAs coding TCR/CD3 chains, including TCRα, TCRβ, CD3γ, CD3δ and CD3ε, as well as the amount of CD3ε protein, a major component of the complex, were unaltered. By contrast, a decrease of the mRNAs deriving from the TCRζ gene locus, as well as of the TCRζ protein which is responsible for the membrane expression of the TCR/CD3 complex, was induced.

These data suggest that the down-modulation of TCR expression is due to the diminution of TCRζ gene products in DEX-treated cells. (Mol Cell Biochem 167: 135-144, 1997)

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Cupps TR, Fauci AS: Corticosteroid-mediated immunoregulation in man. Immunol Rev 65: 133–149, 1982

    Google Scholar 

  2. Barnes PJ, Adckock I: Anti-inflammatory actions of steroids: molecular mechanisms. Trends Pharmacol Sci 14: 436–441, 1993

    Google Scholar 

  3. Hoffman GS: Immunosuppressive therapy for autoimmune diseases. Ann Allergy 70: 263–274, 1993

    Google Scholar 

  4. Beato M: Gene regulation by steroid hormones. Cell 56: 335–344, 1989

    Google Scholar 

  5. Re F, Muzio M, De Rossi M, Polentarutti N, Giri JG, Mantovani A, Colotta F: The type II receptor as a decoy target for interleukin 1 in polymorphonuclear leukocytes: characterization of induction by dex-amethasone and ligand binding properties of the released decoy receptor. J Exp Med 179: 739–743, 1994

    Google Scholar 

  6. DiRosa M, Calignano A, Carnuccio R, Ialenti A, Sautebin L: Multiple control of inflammation by glucocorticoids. Agents Actions 17: 284–288, 1985

    Google Scholar 

  7. Cronstein BN, Kimmel SC, Levin Rl, Martiniuk F, Weissmann G: A mechanism for the antiinflammatory effects of corticosteroids: the glu-cocorticoid receptor regulates leukocyte adhesion to endothelial cells and expression on endothelial-leukocyte adhesion molecule 1 and inter-cellular adhesion molecule 1. Proc Natl Acad Sci USA 89: 9991–9995, 1992

    Google Scholar 

  8. Weiss A, Littman DR: Signal transduction by lymphocyte antigen receptors. Cell 76: 263–274, 1994

    Google Scholar 

  9. Clevers H, Alarcon B, Wileman T, Terhorst C: The T-cell receptor/ CD3 complex: a dynamic protein ensemble. Annul Rev Immunol 6: 629–662, 1988

    Google Scholar 

  10. Weiss A: Molecular and genetic insights into T cell antigen receptor structure and function. Annul Rev Genet 25: 487–510, 1991

    Google Scholar 

  11. Gold DP, Van Dongen JJM, Morton CC, Brun GAP, Van Den Elsen P, Van Kessel Ad HMG, Terhorst C: The gene encoding the subunits of the T3/T-cell receptor complex maps to chromosome 11 in humans and to chromosome 9 in mice. Proc Natl Acad Sci USA 84: 1664–1668, 1987

    Google Scholar 

  12. Gold DP, Clevers H, Alarcon B, Dunlap S, Novotny J, Williams FS, Terhorst C: Evolutionary relationship between the T3 chains of the T-cell receptor complex and the immunoglobulin supergene family. Proc Natl Acad Sci USA 84: 7649–7653, 1987

    Google Scholar 

  13. Blumberg R.S., Ley S., Sancho J., Lonberg N., Lacy E., McDermott F., Schad V., Greenstein J.L., Terhorst C: Structure of the T-cell anti-gen receptor: evidence for two CD3ɛsubunits in T-cell receptor CD3 complex. Proc Natl Acad Sci USA 87: 7220–7224, 1990

    Google Scholar 

  14. Baniyash M, Hsu VW, Seldin MF, Klausner RD: The isolation and characterization of the murine T cell antigen receptor ζchain gene. J Biol Chem 264: 13252–13257, 1988

    Google Scholar 

  15. Weissman AM, Hou D, Orloff DG, Modi WS, Seuanez H, O'Brien SJ, Klausner RD: Molecular cloning and chromosomal localization of the human T-cell receptor ζchain: distinction from the molecular CD3 complex. Proc Natl Acad Sci 85: 9709–9713, 1988

    Google Scholar 

  16. Clayton LK, Diener AC, Lerner A, Tse AGD, Koyasu S, Reinherz EL: Differential regulation of T-cell receptor processing and surface ex-pression affected by CD3θ, an alternatively spliced product of the CD3ζ/ ηgene locus. J Biol Chem 25: 26023–26030, 1992

    Google Scholar 

  17. Clayton LK, D'Adamio L, Howard FD, Sieh M, Hussey RE, Koyasu S, Reinherz EL: CD3ηand CD3ζare alternatively spliced products of a common genetic locus and are transcriptionally and/or post-transcriptionally regulated during T-cell development. Proc Natl Acad Sci USA 88: 5202–5206, 1991

    Google Scholar 

  18. Baniyash M., Garcia-Morales P., Bonifacino J.S., Samelson L.E., Klausner R.D: Disulfide linkage of the ζand ηchains of the T cell receptor. Possible identification of two structural classes of receptors. J Biol Chem 263:9874–9878, 1988

    Google Scholar 

  19. Sussman JJ, Bonifacino JS, Schwartz JL, Weissman AM, Saito T, Klausner RD, Ashwell JD: Failure to synthesize the T cell CD3-zeta chain: structure and function of a partial T cell receptor complex. Cell 52: 85–95, 1988

    Google Scholar 

  20. Weissman AM, Frank SJ, Orloff DG, Mercep M, Ashwell JD, Klausner RD: Role of the zeta chain in the expression of the T cell antigen receptor: genetic reconstitution studies. EMBO J 8: 3651–3656, 1989

    Google Scholar 

  21. Irving BA, Weiss A: The cytoplasmic domain of the T cell receptor zeta chain is sufficient to couple to receptor-associated signal trans-duction pathways. Cell 64: 891–901, 1991

    Google Scholar 

  22. Letourneur F, Klausner RD: T-cell and basophil activation through the cytoplasmic tail of T-cell receptor zeta family proteins. Proc Natl Acad Sci USA 88: 8905–8909, 1991

    Google Scholar 

  23. Chan AC, Irving BA, Fraser JD, Weiss A: The zeta chain is associated with a tyrosine kinase and upon T-cell antigen receptor stimulation associates with ZAP-70, a 70 kDa tyrosine phosphoprotein. Proc Natl Acad Sci USA 88: 9166–9170, 1991

    Google Scholar 

  24. Wange RL, Kong ANT, Samelson LE: A tyrosine-phophorylated 70-kDa protein binds a photoaffinity analogue of ATP and associates with both the zeta chain and CD3 components of the activated T cell anti-gen receptor. J Biol Chem 267: 11685–11688, 1992

    Google Scholar 

  25. Shores EW, Huang K, Tran T, Lee E, Grinberg A, Love PE: Role of TCR ζchain in T cell development and selection. Science 266: 1047–1050, 1994

    Google Scholar 

  26. Simonkevtz R, Kappler J, Marrak P, Grey H: Antigen recognition by H-2-restricted T cells. l. Cell free antigen processing. J Exp Med 158: 303–316, 1983

    Google Scholar 

  27. Hopkins SJ, Humphreys M: Simple, sensitive and specific bioassay of IL-1. J Immunol Methods 120: 271–276, 1989

    Google Scholar 

  28. Cherwinski H, Cshumacher J, Brown K, Mosmann T: Two types of mouse helper T clone. lIl Further differences in lymphokine synthesis between Th1 and Th2 clones. J Exp Med 166: 1229–1244, 1987

    Google Scholar 

  29. Migliorati G, Nicoletti I, Pagliacci MC, D'Adamio L, Riccardi C: Interleukin-4 protects double-negative and CD4 single-positive thymocytes from dexamethasone-induced apoptosis. Blood 81: 1352–1358, 1993

    Google Scholar 

  30. Orloff DG, Frank SJ, Robey FA, Weissman AM, Klausner RD: Bio-chemical characterization of the ηchain of the T-cell receptor. J Biol Chem 264: 14812–14817, 1989

    Google Scholar 

  31. BD Hames and SJ Higgins (eds): Transcription and translation: a practical approach. IRL Press, Oxford, 1985

    Google Scholar 

  32. Migliorati G, Nicoletti I, Nocentini G, Pagliacci MC, Riccardi C: Dex-amethasone and interleukins modulate apoptosis of murine thymocytes. and peripheral T-lymphocytes. Pharmacol Res 30: 43–52, 1994

    Google Scholar 

  33. Sierra-Honigmann MR, Murphy PA: T cell receptor-independent im-munosuppression induced by dexamethasone in murine T helper cells. J Clin Invest 89: 556–560, 1992

    Google Scholar 

  34. Kishimoto H, Surh CD, Sprent J: Upregulation of surface markers on dying thymocytes. J Exp Med 181: 649–655, 1995

    Google Scholar 

  35. Kern JA, Lamb RJ, Reed JL, Daniele RP, Nowell PL: Dexamethasone inhibition of interleukin 1 beta production by human monocytes. Posttranscriptional mechanisms. J Clin Invest 81: 237–244, 1988

    Google Scholar 

  36. Mizoguchi H, O'shea JJ, Longo DL, Loeffler CM, McVicar DW, Ochoa AC: Alterations in signal trasduction molecules in T Iymphocytes from tumor-bearing mice. Science 258: 1795–1798, 1992

    Google Scholar 

  37. Aoe T, Okamoto Y, Saito T: Activated macrophages induce structural abnormalities of the T cell receptor-CD3 complex. J Exp Med 181:1881–1886, 1995

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Clinical Medicine, Pathology and Pharmacology, University of Perugia, 06100, Perugia, Italy

    Graziella Migliorati, Andrea Bartoli, Giuseppe Nocentini, Simona Ronchetti, Rosalba Moraca & Carlo Riccardi

Authors
  1. Graziella Migliorati
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andrea Bartoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Giuseppe Nocentini
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Simona Ronchetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rosalba Moraca
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Carlo Riccardi
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Migliorati, G., Bartoli, A., Nocentini, G. et al. Effect of dexamethasone on T-cell receptor/CD3 expression. Mol Cell Biochem 167, 135–144 (1997). https://doi.org/10.1023/A:1006829421509

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1006829421509

Search

Navigation