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. 1991 Apr;29(4):753–756. doi: 10.1128/jcm.29.4.753-756.1991

Francisella tularensis-induced in vitro gamma interferon, tumor necrosis factor alpha, and interleukin 2 responses appear within 2 weeks of tularemia vaccination in human beings.

R Karttunen 1, H M Surcel 1, G Andersson 1, H P Ekre 1, E Herva 1
PMCID: PMC269865  PMID: 1909711

Abstract

Cell-mediated immunity is essential for protection against the intracellular bacterium Francisella tularensis, which causes tularemia. Positive in vitro T-cell responses in the form of lymphocyte proliferation and lymphokine interleukin 2 (IL-2) and gamma interferon (IFN-gamma) secretion are found in memory immunity. Studies on the secretion of lymphokines with regard to the developing immunity to F. tularensis have not been published. Therefore, 14 subjects with no clinical history of tularemia were vaccinated with a live F. tularensis vaccine strain. The in vitro responses of five subjects (antigen-induced mononuclear cell and whole blood culture DNA synthesis and cytokine secretion) were measured twice a week throughout the period from 0 to 35 days after vaccination, and the peripheral blood lymphocyte subpopulations of nine subjects were determined between days 0 and 14. Positive reactions, i.e., responses exceeding those on day 0, were reached on day 10 with regard to the whole blood culture DNA synthesis response and IL-2 and IFN-gamma secretion and on day 14 with regard to the mononuclear cell DNA synthesis response and tumor necrosis factor alpha (TNF-alpha) secretion. No measurable IL-4 was found in either the immune or nonimmune supernatants. Since the secretion of TNF-alpha was related to immunization, this points to the specificity of the phenomenon, even though the type of secreting cell is not yet known. If it is shown later that specific T cells produce it, the TNF-alpha response and the negative IL-4 finding may speak for the importance of the Th1-like pattern in immunity to F. tularensis.

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Selected References

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  1. Andersson G., Ekre H. P., Alm G., Perlmann P. Monoclonal antibody two-site ELISA for human IFN-gamma. Adaptation for determinations in human serum or plasma. J Immunol Methods. 1989 Dec 20;125(1-2):89–96. doi: 10.1016/0022-1759(89)90081-1. [DOI] [PubMed] [Google Scholar]
  2. Andersson U., Matsuda T. Human interleukin 6 and tumor necrosis factor alpha production studied at a single-cell level. Eur J Immunol. 1989 Jun;19(6):1157–1160. doi: 10.1002/eji.1830190629. [DOI] [PubMed] [Google Scholar]
  3. Balkwill F. R., Burke F. The cytokine network. Immunol Today. 1989 Sep;10(9):299–304. doi: 10.1016/0167-5699(89)90085-6. [DOI] [PubMed] [Google Scholar]
  4. Cuturi M. C., Murphy M., Costa-Giomi M. P., Weinmann R., Perussia B., Trinchieri G. Independent regulation of tumor necrosis factor and lymphotoxin production by human peripheral blood lymphocytes. J Exp Med. 1987 Jun 1;165(6):1581–1594. doi: 10.1084/jem.165.6.1581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hackett R. J., Davis L. S., Lipsky P. E. Comparative effects of tumor necrosis factor-alpha and IL-1 beta on mitogen-induced T cell activation. J Immunol. 1988 Apr 15;140(8):2639–2644. [PubMed] [Google Scholar]
  6. Heidenreich S., Weyers M., Gong J. H., Sprenger H., Nain M., Gemsa D. Potentiation of lymphokine-induced macrophage activation by tumor necrosis factor-alpha. J Immunol. 1988 Mar 1;140(5):1511–1518. [PubMed] [Google Scholar]
  7. Karttunen R., Andersson G., Ekre H. P., Juutinen K., Surcel H. M., Syrjälä H., Herva E. Interleukin 2 and gamma interferon production, interleukin 2 receptor expression, and DNA synthesis induced by tularemia antigen in vitro after natural infection or vaccination. J Clin Microbiol. 1987 Jun;25(6):1074–1078. doi: 10.1128/jcm.25.6.1074-1078.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Karttunen R., Ilonen J., Herva E. Interleukin 2 production in whole blood culture: a rapid test of immunity to Francisella tularensis. J Clin Microbiol. 1985 Aug;22(2):318–319. doi: 10.1128/jcm.22.2.318-319.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Mosmann T. R., Cherwinski H., Bond M. W., Giedlin M. A., Coffman R. L. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986 Apr 1;136(7):2348–2357. [PubMed] [Google Scholar]
  10. Owen-Schaub L. B., Crump W. L., 3rd, Morin G. I., Grimm E. A. Regulation of lymphocyte tumor necrosis factor receptors by IL-2. J Immunol. 1989 Oct 1;143(7):2236–2241. [PubMed] [Google Scholar]
  11. Patel S. S., Duby A. D., Thiele D. L., Lipsky P. E. Phenotypic and functional characterization of human T cell clones. J Immunol. 1988 Dec 1;141(11):3726–3736. [PubMed] [Google Scholar]
  12. Pawelec G. P., Rehbein A., Schaudt K., Busch F. W. IL-4-responsive human helper T cell clones are resistant to growth inhibition by tumor necrosis factor-alpha. J Immunol. 1989 Aug 1;143(3):902–906. [PubMed] [Google Scholar]
  13. Pawelec G., Schaudt K., Rehbein A., Busch F. W. Differential secretion of tumor necrosis factor-alpha and granulocyte/macrophage colony-stimulating factors but not interferon-gamma from CD4+ compared to CD8+ human T cell clones. Eur J Immunol. 1989 Jan;19(1):197–200. doi: 10.1002/eji.1830190132. [DOI] [PubMed] [Google Scholar]
  14. Scheurich P., Thoma B., Ucer U., Pfizenmaier K. Immunoregulatory activity of recombinant human tumor necrosis factor (TNF)-alpha: induction of TNF receptors on human T cells and TNF-alpha-mediated enhancement of T cell responses. J Immunol. 1987 Mar 15;138(6):1786–1790. [PubMed] [Google Scholar]
  15. Shalaby M. R., Espevik T., Rice G. C., Ammann A. J., Figari I. S., Ranges G. E., Palladino M. A., Jr The involvement of human tumor necrosis factors-alpha and -beta in the mixed lymphocyte reaction. J Immunol. 1988 Jul 15;141(2):499–503. [PubMed] [Google Scholar]
  16. Steffen M., Ottmann O. G., Moore M. A. Simultaneous production of tumor necrosis factor-alpha and lymphotoxin by normal T cells after induction with IL-2 and anti-T3. J Immunol. 1988 Apr 15;140(8):2621–2624. [PubMed] [Google Scholar]
  17. Street N. E., Schumacher J. H., Fong T. A., Bass H., Fiorentino D. F., Leverah J. A., Mosmann T. R. Heterogeneity of mouse helper T cells. Evidence from bulk cultures and limiting dilution cloning for precursors of Th1 and Th2 cells. J Immunol. 1990 Mar 1;144(5):1629–1639. [PubMed] [Google Scholar]
  18. Sung S. S., Bjorndahl J. M., Wang C. Y., Kao H. T., Fu S. M. Production of tumor necrosis factor/cachectin by human T cell lines and peripheral blood T lymphocytes stimulated by phorbol myristate acetate and anti-CD3 antibody. J Exp Med. 1988 Mar 1;167(3):937–953. doi: 10.1084/jem.167.3.937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Surcel H. M. Diversity of Francisella tularensis antigens recognized by human T lymphocytes. Infect Immun. 1990 Aug;58(8):2664–2668. doi: 10.1128/iai.58.8.2664-2668.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Surcel H. M., Ilonen J., Poikonen K., Herva E. Francisella tularensis-specific T-cell clones are human leukocyte antigen class II restricted, secrete interleukin-2 and gamma interferon, and induce immunoglobulin production. Infect Immun. 1989 Sep;57(9):2906–2908. doi: 10.1128/iai.57.9.2906-2908.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Tärnvik A. Nature of protective immunity to Francisella tularensis. Rev Infect Dis. 1989 May-Jun;11(3):440–451. [PubMed] [Google Scholar]
  22. Yokota S., Geppert T. D., Lipsky P. E. Enhancement of antigen- and mitogen-induced human T lymphocyte proliferation by tumor necrosis factor-alpha. J Immunol. 1988 Jan 15;140(2):531–536. [PubMed] [Google Scholar]

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