Role of Interferon Gamma in the Priming of Human Accessory Cells for Autocrine Secretion of Monokines (IL-1 and TNF) and HLA Class II Gene Expression

  • J. L. Virelizier
  • F. Arenzana-Seisdedos
  • S. C. Mogensen
Part of the NATO ASI Series book series (NSSA, volume 179)


Vaccine preparations of the future are likely to use as antigens recombinant proteins or synthetic peptides rather than whole micro-organisms. This implies the use of adjuvants to increase the poor immunogenicity of such molecules for both antibody and T lymphocyte responses. The mechanism of action of adjuvants is complex and not entirely understood, but is likely to be associated with increased antigen-presenting ability of specialized cell types such as monocyte-macrophage or dendritic cells. It is apparent that an essential step in the induction of responsiveness to foreign proteins is the activation of helper T lymphocytes after specific recognition of relevant epitopes on the membrane of antigen-presenting cells (APC). The aim of the present communication is not to review the complex events associated with antigen presentation, and the reader is referred to excellent reviews by Uhanue et al, 1984 and Germain, 1986. Rather, we will discuss regulation of some properties of APC by exogenous lymphokines such as interferon (IFN) gamma, and the role of autocrine secretion of monokines in IFN gamma-induced macrophage activation and HLA class II gene expression, two essential requirements for efficient antigen presentation (Kurt-Jones et al, 1985).


U937 Cell Monocytic Cell Line Secretory Potential Autocrine Secretion Tumor Necrosis Factor Secretion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Arenzana-Seisdedos, F., Virelizier, J.L. and Fiers, W., 1985, Interferons as macrophage-activating factors. III. Preferential effects of interferon gamma on the interleukin 1 secretory potential of fresh or aged human monocytes, J. Immunol., 134: 2444.PubMedGoogle Scholar
  2. Arenzana-Seisdedos, F., Barbey, S., Virelizier, J.L., Kornprobst, M. and Nezelof, C., 1986, Histocytosis X: Purified (T6+) cells from bone granuloma produce interleukin 1 and prostaglandin E2 in culture, J.Clin.Invest., 77: 326.PubMedCrossRefGoogle Scholar
  3. Arenzana-Seisdedos, F., Mogensen, S.C., Vuillier, F., Fiers, W. and Virelizier, J.L., 1988, Autocrine secretion of tumor necrosis factor under the influence of interferon-gamma amplifies HLA-DR gene induction in human monocytes, Proc.Natl.Acad.Sci.USA, 85: 000.CrossRefGoogle Scholar
  4. Bjerck, S., Elgo, J., Braathen, L. and Thorsby, E., 1984, Enriched epidermal Langerhans cells are potent antigen-presenting cells for T cells, J.Invest.Dermatol., 77: 286.CrossRefGoogle Scholar
  5. Burchett, S.K., Weaver, W.M., Westall, J.A., Larsen, A., Kronheim, S. and Wilson, C.B., 1988, Regulation of tumor necrosis factor-cachectin and IL-1 secretion in human mononuclear phagocytes, J. Immunol., 140: 3473.PubMedGoogle Scholar
  6. Chang, R.J. and Lee, S.H., 1986, Effects of interferon-gamma and tumor necrosis factor on the expression of an Ia antigen on a murine macrophage cell line, J. Immunol., 137: 2853.PubMedGoogle Scholar
  7. Collart, M.A., Belin, D., Vassalli, J.D., de Kossodo, S. and Vassalli, P., 1986, Gamma interferon enhances macrophage transcription of the tumor necrosis factor-cachectin, interleukin 1 and urokinase genes, which are controlled by short-lives repressors, J.Exp.Med., 164: 2113.PubMedCrossRefGoogle Scholar
  8. Collins, T., Lapierre, L.A., Fiers, W., Strominger, J.L. and Pober, J.S., 1986, Recombinant human tumor necrosis factor increase mRNA levels and surface expression of HLA-A-B antigens in vascular endothelial cells and dermal fibroblasts in vitro, Proc.Natl.Acad.Sci.USA, 83: 446.PubMedCrossRefGoogle Scholar
  9. Germain, R.N., 1986, The ins and outs of antigen processing and presentation, Nature, 322: 687.PubMedCrossRefGoogle Scholar
  10. Grob, P.J., Joller-Jemelka, H.I., Binswanger, V., Zaruba, K., Descoendres, C. and Fernex, M., 1984, Interferon as an adjuvant for hepatitis B vaccination in non-and low responder populations, Eur.J.Clin. Microbiol., 3: 195.PubMedCrossRefGoogle Scholar
  11. Inaba, K. and Steinman, R.M., 1984, Resting and sensitized T lymphocytes exhibit distinct stimulatory (antigen-presenting cells) requirements for growth and lymphokine release, J.Exp.Med., 160: 1717.PubMedCrossRefGoogle Scholar
  12. Kurt-Jones, E.A., Virgin, H.W. and Uhanu, E.R., 1985, Relationship of macrophage Ia and membrane IL-1 expression to antigen presentation, J. Immunol., 135: 3652.PubMedGoogle Scholar
  13. Lechler, R.I., Norcross, M.A. and Germain, R.N., 1985, Qualitative and quantitative studies of antigen-presenting cell function by using I-A expressing L cells, J. Immunol., 135: 2914.PubMedGoogle Scholar
  14. Matis, L.A., Glimcher, L.H., Paul, W.E. and Schwartz, R.H., 1983, Magnitude of response of histocompatibility-restricted T cell clones is a function of the concentration of antigen and Ia molecules, Proc.Natl. Acad.Sci.USA, 80: 6019.PubMedCrossRefGoogle Scholar
  15. Nakumura, M., Mauser, T., Pearson, G.D.N., Daley, M.J. and Gefter, M.L., 1984, Effect of IFN-gamma on the immune response in vivo and on gene expression in vitro, Nature, 307: 381.Google Scholar
  16. Philip, R. and Epstein, L., 1986, Tumor necrosis factor as immunomodulator and mediator of monocyte cytotoxicity induced by itself, interferon and interleukin 1, Nature, 323: 86.PubMedCrossRefGoogle Scholar
  17. Rosa, F. and Fellous, M., 1984, The effect of gamma-interferon on MHC antigens, Immunol.Today, 5: 261.CrossRefGoogle Scholar
  18. Shimada, S., Canghman, W., Sharrow, S.O., Stephany, D. and Katz, S.I., 1987, Enhanced antigen-presenting capacity of cultured Langerhans cells is associated with markedly increased expression of Ia antigen, J. Immunol., 139: 2551.PubMedGoogle Scholar
  19. Sztein, M.B., Steeg, P.S., Johnson, H.M. and Oppenheim, J.J., 1984, Regulation of human peripheral blood monocyte DR antigen expression in vitro by lymphokines and recombinant interferons, J. Clin.Invest., 73: 556.PubMedCrossRefGoogle Scholar
  20. Teyton, L., Lotteau, V., Turmel, P., Arenzana-Seisdedos, F., Virelizier, J.L., Pujol, J.P., Loyau, G., Piattier-Tonneau, D., Auffray, C. and Charron, D., 1987, HLA-DR, DQ and DP antigen expression in rheumatoid synovial cells: a biochemical and quantitative study, J. Immunol., 138: 1730.PubMedGoogle Scholar
  21. Uhanue, E.R., Beller, D.I., Lu, C.Y. and Allen, P.M., 1984, Antigen presentation: Comments on its regulation and mechanism, J. Immunol., 132: 1.Google Scholar
  22. Virelizier, J.L., Perez, N., Arenzana-Seisdedos, F. and Devos, R., 1984, Pure interferon-gamma enhances class II HLA antigens on human monocyte cell lines, Eur.J. Immunol., 14: 106.PubMedCrossRefGoogle Scholar
  23. Walker, E.B., Maino, V., Sanchez-Lanier, M., Warner, N. and Stewart, C., 1984, Murine gamma interferon activates the release of a macrophagederived Ia inducing factor that transfers Ia inductive capacity, J.Exp.Med., 159: 1532.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • J. L. Virelizier
    • 1
  • F. Arenzana-Seisdedos
    • 1
  • S. C. Mogensen
    • 2
  1. 1.Laboratoire d’Immunologie ViraleInstitut PasteurParisFrance
  2. 2.Institute of Medical MicrobiologyUniversity of AarhusAarhusDenmark

Personalised recommendations