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. 1986 Aug;65(2):387–395.

Glucocorticoid enhances gamma interferon effects on human monocyte antigen expression and ADCC.

L Shen, P M Guyre, E D Ball, M W Fanger
PMCID: PMC1542299  PMID: 3098477

Abstract

The expression of HLA-DR antigen by highly enriched human monocytes cultured in serum free medium was found to be markedly elevated by human recombinant gamma interferon (IFN-gamma). This effect was maximal after 48 h in culture with 300 mu/ml IFN-gamma. Class I MHC antigen also increased with IFN-gamma treatment. By contrast, binding of a myeloid-specific monoclonal antibody, AML-2-23, was dramatically decreased by IFN-gamma. The augmentation of MHC antigens was not ablated by an immunosuppressive concentration (2 X 10(-7) M) of the glucocorticoid dexamethasone (DEX). In fact, both the enhancement of Class I and Class II MHC antigen expression and the suppression of AML-2-23 antigen by IFN-gamma were often more profound in the presence of DEX. IFN-gamma treatment also resulted in elevated monocyte effector function, as measured by antibody dependent cellular cytotoxicity (ADCC). This functional activation was not inhibited by DEX. On the contrary, DEX slightly augmented IFN-gamma effects on ADCC. This contrasts with other reports that glucocorticoids inhibit monocyte responsiveness to lymphokines, and suggests that the interplay between lymphokines and the glucocorticoid hormones may be more complex than previously thought.

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Selected References

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

  1. Arya S. K., Wong-Staal F., Gallo R. C. Dexamethasone-mediated inhibition of human T cell growth factor and gamma-interferon messenger RNA. J Immunol. 1984 Jul;133(1):273–276. [PubMed] [Google Scholar]
  2. Baker P. E., Knoblock K. F. Bovine costimulator. I. Production kinetics, partial purification, and quantification in serum-free Iscove's medium. Vet Immunol Immunopathol. 1982 Jul;3(4):365–379. doi: 10.1016/0165-2427(82)90020-4. [DOI] [PubMed] [Google Scholar]
  3. Ball E. D., Graziano R. F., Shen L., Fanger M. W. Monoclonal antibodies to novel myeloid antigens reveal human neutrophil heterogeneity. Proc Natl Acad Sci U S A. 1982 Sep;79(17):5374–5378. doi: 10.1073/pnas.79.17.5374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Basham T. Y., Merigan T. C. Recombinant interferon-gamma increases HLA-DR synthesis and expression. J Immunol. 1983 Apr;130(4):1492–1494. [PubMed] [Google Scholar]
  5. Beller D. I., Ho K. Regulation of macrophage populations. V. Evaluation of the control of macrophage Ia expression in vitro. J Immunol. 1982 Sep;129(3):971–976. [PubMed] [Google Scholar]
  6. Crabtree G. R., Munck A., Smith K. A. Glucocorticoids inhibit expression of Fc receptors on the human granulocytic cell line HL-60. Nature. 1979 May 24;279(5711):338–339. doi: 10.1038/279338a0. [DOI] [PubMed] [Google Scholar]
  7. Cupps T. R., Fauci A. S. Corticosteroid-mediated immunoregulation in man. Immunol Rev. 1982;65:133–155. doi: 10.1111/j.1600-065x.1982.tb00431.x. [DOI] [PubMed] [Google Scholar]
  8. Doherty P. C., Blanden R. V., Zinkernagel R. M. Specificity of virus-immune effector T cells for H-2K or H-2D compatible interactions: implications for H-antigen diversity. Transplant Rev. 1976;29:89–124. doi: 10.1111/j.1600-065x.1976.tb00198.x. [DOI] [PubMed] [Google Scholar]
  9. Evans R., Alexander P. Role of macrophages in tumour immunity. II. Involvement of a macrophage cytophilic factor during syngeneic tumour growth inhibition. Immunology. 1972 Oct;23(4):627–636. [PMC free article] [PubMed] [Google Scholar]
  10. Germain R. N., Dorf M. E., Benacerraf B. Inhibition of T-lymphocyte-mediated tumor-specific lysis by alloantisera directed against the H-2 serological specificities of the tumor. J Exp Med. 1975 Oct 1;142(4):1023–1028. doi: 10.1084/jem.142.4.1023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gerrard T. L., Cupps T. R., Jurgensen C. H., Fauci A. S. Increased expression of HLA-DR antigens in hydrocortisone-treated monocytes. Cell Immunol. 1984 Apr 1;84(2):311–316. doi: 10.1016/0008-8749(84)90102-3. [DOI] [PubMed] [Google Scholar]
  12. Gillis S., Crabtree G. R., Smith K. A. Glucocorticoid-induced inhibition of T cell growth factor production. I. The effect on mitogen-induced lymphocyte proliferation. J Immunol. 1979 Oct;123(4):1624–1631. [PubMed] [Google Scholar]
  13. Gray P. W., Leung D. W., Pennica D., Yelverton E., Najarian R., Simonsen C. C., Derynck R., Sherwood P. J., Wallace D. M., Berger S. L. Expression of human immune interferon cDNA in E. coli and monkey cells. Nature. 1982 Feb 11;295(5849):503–508. doi: 10.1038/295503a0. [DOI] [PubMed] [Google Scholar]
  14. Guyre P. M., Bodwell J. E., Munck A. Glucocorticoid actions on the immune system: inhibition of production of an Fc-receptor augmenting factor. J Steroid Biochem. 1981 Dec;15:35–39. doi: 10.1016/0022-4731(81)90255-7. [DOI] [PubMed] [Google Scholar]
  15. Guyre P. M., Morganelli P. M., Miller R. Recombinant immune interferon increases immunoglobulin G Fc receptors on cultured human mononuclear phagocytes. J Clin Invest. 1983 Jul;72(1):393–397. doi: 10.1172/JCI110980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Johnston R. B., Jr Oxygen metabolism and the microbicidal activity of macrophages. Fed Proc. 1978 Nov;37(13):2759–2764. [PubMed] [Google Scholar]
  17. Maliszewski C. R., Ball E. D., Graziano R. F., Fanger M. W. Isolation and characterization of My23, a myeloid cell-derived antigen reactive with the monoclonal antibody AML-2-23. J Immunol. 1985 Sep;135(3):1929–1936. [PubMed] [Google Scholar]
  18. Mantovani A., Caprioli V., Gritti P., Spreafico F. Human mature macrophages mediate antibody-dependent cellular cytotoxicity on tumour cells. Transplantation. 1977 Oct;24(4):291–293. doi: 10.1097/00007890-197710000-00010. [DOI] [PubMed] [Google Scholar]
  19. Munck A., Guyre P. M., Holbrook N. J. Physiological functions of glucocorticoids in stress and their relation to pharmacological actions. Endocr Rev. 1984 Winter;5(1):25–44. doi: 10.1210/edrv-5-1-25. [DOI] [PubMed] [Google Scholar]
  20. Normann S. J., Weiner R. Cytotoxicity of human peripheral blood monocytes. Cell Immunol. 1983 Oct 15;81(2):413–425. doi: 10.1016/0008-8749(83)90248-4. [DOI] [PubMed] [Google Scholar]
  21. Raff H. V., Picker L. J., Stobo J. D. Macrophage heterogeneity in man. A subpopulation of HLA-DR-bearing macrophages required for antigen-induced T cell activation also contains stimulators for autologous-reactive T cells. J Exp Med. 1980 Sep 1;152(3):581–593. doi: 10.1084/jem.152.3.581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Reinherz E. L., Kung P. C., Pesando J. M., Ritz J., Goldstein G., Schlossman S. F. Ia determinants on human T-cell subsets defined by monoclonal antibody. Activation stimuli required for expression. J Exp Med. 1979 Dec 1;150(6):1472–1482. doi: 10.1084/jem.150.6.1472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Scher M. G., Beller D. I., Unanue E. R. Demonstration of a soluble mediator that induces exudates rich in Ia-positive macrophages. J Exp Med. 1980 Dec 1;152(6):1684–1698. doi: 10.1084/jem.152.6.1684. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Shen L., Guyre P. M., Fanger M. W. Direct stimulation of ADCC by cloned gamma interferon is not ablated by glucocorticoids: studies using a human monocyte-like cell line (U-937). Mol Immunol. 1984 Feb;21(2):167–173. doi: 10.1016/0161-5890(84)90132-9. [DOI] [PubMed] [Google Scholar]
  25. Silberman H. Dosage of corticosteroids in renal allograft rejection. Am J Surg. 1981 Sep;142(3):413–415. doi: 10.1016/0002-9610(81)90363-9. [DOI] [PubMed] [Google Scholar]
  26. Stanwick T. L., Campbell D. E., Nahmias A. J. Cytotoxic properties of human monocyte-macrophages for human fibroblasts infected in herpes simplex virus: interferon production and augmentation. Cell Immunol. 1982 Jun;70(1):132–147. doi: 10.1016/0008-8749(82)90139-3. [DOI] [PubMed] [Google Scholar]
  27. Ugolini V., Nunez G., Smith R. G., Stastny P., Capra J. D. Initial characterization of monoclonal antibodies against human monocytes. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6764–6768. doi: 10.1073/pnas.77.11.6764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Warren M. K., Vogel S. N. Opposing effects of glucocorticoids on interferon-gamma-induced murine macrophage Fc receptor and Ia antigen expression. J Immunol. 1985 Apr;134(4):2462–2469. [PubMed] [Google Scholar]
  29. Wright S. D., Silverstein S. C. Tumor-promoting phorbol esters stimulate C3b and C3b' receptor-mediated phagocytosis in cultured human monocytes. J Exp Med. 1982 Oct 1;156(4):1149–1164. doi: 10.1084/jem.156.4.1149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Yamashita U., Shevach E. M. The expression of Ia antigens on immunocompetent cells in the guinea pig. II. Ia antigens on macrophages. J Immunol. 1977 Nov;119(5):1584–1588. [PubMed] [Google Scholar]

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