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. 1995 Mar;63(3):1107–1112. doi: 10.1128/iai.63.3.1107-1112.1995

TH1 cells trigger tumor necrosis factor alpha-mediated hypersensitivity to Pseudomonas aeruginosa after adoptive transfer into SCID mice.

R Früh 1, B Blum 1, H Mossmann 1, H Domdey 1, B U von Specht 1
PMCID: PMC173117  PMID: 7868234

Abstract

Recent experiments have shown that gamma interferon (IFN-gamma), either administered or induced in vivo, e.g., by certain bacteria, is a key mediator in inducing hypersensitivity to bacterial lipopolysaccharides. The source of endogenous IFN-gamma in this context (natural killer versus TH1 cells) has not been investigated yet. In order to investigate the role of antigen-specific, IFN-gamma-producing TH1 cells in murine Pseudomonas aeruginosa infection, a murine TH1 cell line was propagated in vitro by using recombinant P. aeruginosa outer membrane protein I. Adoptive transfer experiments were performed by intravenous injection of various amounts of TH1 cells into P. aeruginosa-challenged SCID mice. Adoptive transfer of 5 x 10(6) T cells into SCID mice followed by an intraperitoneal challenge with 1.4 x 10(6) CFU of live P. aeruginosa resulted in the rapid death of the animals within 12 h postchallenge, whereas transfer of lower T-cell doses and saline as a control did not cause any detrimental effects. After challenge with 2.8 x 10(6) CFU of P. aeruginosa, similar results were obtained 18 h postchallenge; however, at the end of the 72-h observation period, no significant differences in survival rates were obtained between the groups treated with different amounts of T cells. The rapid death of mice treated with 5 x 10(6) T cells was reflected by 860-fold-elevated levels of tumor necrosis factor alpha (TNF-alpha) present in serum 2 h postchallenge, whereas no significant differences in TNF-alpha serum levels were detectable in mice treated with lower doses of T cells or with saline. Pretreatment of T-cell-reconstituted SCID mice with neutralizing anti-IFN-gamma monoclonal antibodies completely protected mice from bacterial challenge and reduced TNF-alpha levels in serum. We conclude that under the experimental conditions described here, IFN-gamma- and interleukin-2-producing TH1 cells represent an important trigger mechanism inducing TNF-alpha-mediated hypersensitivity to bacterial endotoxin.

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Selected References

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  1. Aggarwal B. B., Eessalu T. E., Hass P. E. Characterization of receptors for human tumour necrosis factor and their regulation by gamma-interferon. Nature. 1985 Dec 19;318(6047):665–667. doi: 10.1038/318665a0. [DOI] [PubMed] [Google Scholar]
  2. Aggarwal B. B., Kohr W. J., Hass P. E., Moffat B., Spencer S. A., Henzel W. J., Bringman T. S., Nedwin G. E., Goeddel D. V., Harkins R. N. Human tumor necrosis factor. Production, purification, and characterization. J Biol Chem. 1985 Feb 25;260(4):2345–2354. [PubMed] [Google Scholar]
  3. Bancroft G. J., Schreiber R. D., Bosma G. C., Bosma M. J., Unanue E. R. A T cell-independent mechanism of macrophage activation by interferon-gamma. J Immunol. 1987 Aug 15;139(4):1104–1107. [PubMed] [Google Scholar]
  4. Bancroft G. J., Sheehan K. C., Schreiber R. D., Unanue E. R. Tumor necrosis factor is involved in the T cell-independent pathway of macrophage activation in scid mice. J Immunol. 1989 Jul 1;143(1):127–130. [PubMed] [Google Scholar]
  5. Beutler B., Cerami A. Tumor necrosis, cachexia, shock, and inflammation: a common mediator. Annu Rev Biochem. 1988;57:505–518. doi: 10.1146/annurev.bi.57.070188.002445. [DOI] [PubMed] [Google Scholar]
  6. Beutler B., Milsark I. W., Cerami A. C. Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science. 1985 Aug 30;229(4716):869–871. doi: 10.1126/science.3895437. [DOI] [PubMed] [Google Scholar]
  7. Bosma G. C., Custer R. P., Bosma M. J. A severe combined immunodeficiency mutation in the mouse. Nature. 1983 Feb 10;301(5900):527–530. doi: 10.1038/301527a0. [DOI] [PubMed] [Google Scholar]
  8. Bosma G. C., Davisson M. T., Ruetsch N. R., Sweet H. O., Shultz L. D., Bosma M. J. The mouse mutation severe combined immune deficiency (scid) is on chromosome 16. Immunogenetics. 1989;29(1):54–57. doi: 10.1007/BF02341614. [DOI] [PubMed] [Google Scholar]
  9. Bottomly K. A functional dichotomy in CD4+ T lymphocytes. Immunol Today. 1988 Sep;9(9):268–274. doi: 10.1016/0167-5699(88)91308-4. [DOI] [PubMed] [Google Scholar]
  10. Collart M. A., Belin D., Vassalli J. D., de Kossodo S., Vassalli P. Gamma interferon enhances macrophage transcription of the tumor necrosis factor/cachectin, interleukin 1, and urokinase genes, which are controlled by short-lived repressors. J Exp Med. 1986 Dec 1;164(6):2113–2118. doi: 10.1084/jem.164.6.2113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Corradin G., Etlinger H. M., Chiller J. M. Lymphocyte specificity to protein antigens. I. Characterization of the antigen-induced in vitro T cell-dependent proliferative response with lymph node cells from primed mice. J Immunol. 1977 Sep;119(3):1048–1053. [PubMed] [Google Scholar]
  12. Czitrom A. A., Edwards S., Phillips R. A., Bosma M. J., Marrack P., Kappler J. W. The function of antigen-presenting cells in mice with severe combined immunodeficiency. J Immunol. 1985 Apr;134(4):2276–2280. [PubMed] [Google Scholar]
  13. Dorshkind K., Pollack S. B., Bosma M. J., Phillips R. A. Natural killer (NK) cells are present in mice with severe combined immunodeficiency (scid). J Immunol. 1985 Jun;134(6):3798–3801. [PubMed] [Google Scholar]
  14. Duchêne M., Barron C., Schweizer A., von Specht B. U., Domdey H. Pseudomonas aeruginosa outer membrane lipoprotein I gene: molecular cloning, sequence, and expression in Escherichia coli. J Bacteriol. 1989 Aug;171(8):4130–4137. doi: 10.1128/jb.171.8.4130-4137.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Fitch F. W., McKisic M. D., Lancki D. W., Gajewski T. F. Differential regulation of murine T lymphocyte subsets. Annu Rev Immunol. 1993;11:29–48. doi: 10.1146/annurev.iy.11.040193.000333. [DOI] [PubMed] [Google Scholar]
  16. Freudenberg M. A., Galanos C. Tumor necrosis factor alpha mediates lethal activity of killed gram-negative and gram-positive bacteria in D-galactosamine-treated mice. Infect Immun. 1991 Jun;59(6):2110–2115. doi: 10.1128/iai.59.6.2110-2115.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Galanos C., Freudenberg M. A., Reutter W. Galactosamine-induced sensitization to the lethal effects of endotoxin. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5939–5943. doi: 10.1073/pnas.76.11.5939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Griffith S. J., Nathan C., Selander R. K., Chamberlin W., Gordon S., Kabins S., Weinstein R. A. The epidemiology of Pseudomonas aeruginosa in oncology patients in a general hospital. J Infect Dis. 1989 Dec;160(6):1030–1036. doi: 10.1093/infdis/160.6.1030. [DOI] [PubMed] [Google Scholar]
  19. Handa K., Suzuki R., Matsui H., Shimizu Y., Kumagai K. Natural killer (NK) cells as a responder to interleukin 2 (IL 2). II. IL 2-induced interferon gamma production. J Immunol. 1983 Feb;130(2):988–992. [PubMed] [Google Scholar]
  20. Heinzel F. P. The role of IFN-gamma in the pathology of experimental endotoxemia. J Immunol. 1990 Nov 1;145(9):2920–2924. [PubMed] [Google Scholar]
  21. Heremans H., Dillen C., van Damme J., Billiau A. Essential role for natural killer cells in the lethal lipopolysaccharide-induced Shwartzman-like reaction in mice. Eur J Immunol. 1994 May;24(5):1155–1160. doi: 10.1002/eji.1830240522. [DOI] [PubMed] [Google Scholar]
  22. Heremans H., Van Damme J., Dillen C., Dijkmans R., Billiau A. Interferon gamma, a mediator of lethal lipopolysaccharide-induced Shwartzman-like shock reactions in mice. J Exp Med. 1990 Jun 1;171(6):1853–1869. doi: 10.1084/jem.171.6.1853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hu-Li J., Ohara J., Watson C., Tsang W., Paul W. E. Derivation of a T cell line that is highly responsive to IL-4 and IL-2 (CT.4R) and of an IL-2 hyporesponsive mutant of that line (CT.4S). J Immunol. 1989 Feb 1;142(3):800–807. [PubMed] [Google Scholar]
  24. Inoyye S., Takeishi K., Lee N., DeMartini M., Hirashima A., Inouye M. Lipoprotein from the outer membrane of Escherichia coli: purification, paracrystallization, and some properties of its free form. J Bacteriol. 1976 Jul;127(1):555–563. doi: 10.1128/jb.127.1.555-563.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Katschinski T., Galanos C., Coumbos A., Freudenberg M. A. Gamma interferon mediates Propionibacterium acnes-induced hypersensitivity to lipopolysaccharide in mice. Infect Immun. 1992 May;60(5):1994–2001. doi: 10.1128/iai.60.5.1994-2001.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Korvick J. A., Marsh J. W., Starzl T. E., Yu V. L. Pseudomonas aeruginosa bacteremia in patients undergoing liver transplantation: an emerging problem. Surgery. 1991 Jan;109(1):62–68. [PMC free article] [PubMed] [Google Scholar]
  27. Marget M., Eckhardt A., Ehret W., von Specht B. U., Duchêne M., Domdey H. Cloning and characterization of cDNAs coding for the heavy and light chains of a monoclonal antibody specific for Pseudomonas aeruginosa outer membrane protein I. Gene. 1988 Dec 30;74(2):335–345. doi: 10.1016/0378-1119(88)90167-9. [DOI] [PubMed] [Google Scholar]
  28. Nawroth P. P., Bank I., Handley D., Cassimeris J., Chess L., Stern D. Tumor necrosis factor/cachectin interacts with endothelial cell receptors to induce release of interleukin 1. J Exp Med. 1986 Jun 1;163(6):1363–1375. doi: 10.1084/jem.163.6.1363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Old L. J. Tumor necrosis factor (TNF). Science. 1985 Nov 8;230(4726):630–632. doi: 10.1126/science.2413547. [DOI] [PubMed] [Google Scholar]
  30. Takacs B. J., Girard M. F. Preparation of clinical grade proteins produced by recombinant DNA technologies. J Immunol Methods. 1991 Oct 25;143(2):231–240. doi: 10.1016/0022-1759(91)90048-k. [DOI] [PubMed] [Google Scholar]
  31. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Tracey K. J., Lowry S. F. The role of cytokine mediators in septic shock. Adv Surg. 1990;23:21–56. [PubMed] [Google Scholar]
  33. Tsujimoto M., Yip Y. K., Vilcek J. Interferon-gamma enhances expression of cellular receptors for tumor necrosis factor. J Immunol. 1986 Apr 1;136(7):2441–2444. [PubMed] [Google Scholar]
  34. Van Snick J. Interleukin-6: an overview. Annu Rev Immunol. 1990;8:253–278. doi: 10.1146/annurev.iy.08.040190.001345. [DOI] [PubMed] [Google Scholar]
  35. Van Zee K. J., DeForge L. E., Fischer E., Marano M. A., Kenney J. S., Remick D. G., Lowry S. F., Moldawer L. L. IL-8 in septic shock, endotoxemia, and after IL-1 administration. J Immunol. 1991 May 15;146(10):3478–3482. [PubMed] [Google Scholar]
  36. Wherry J. C., Schreiber R. D., Unanue E. R. Regulation of gamma interferon production by natural killer cells in scid mice: roles of tumor necrosis factor and bacterial stimuli. Infect Immun. 1991 May;59(5):1709–1715. doi: 10.1128/iai.59.5.1709-1715.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. von Specht B. U., Strigl G., Ehret W., Brendel W. Protective effect of an outer membrane vaccine against Pseudomonas aeruginosa infection. Infection. 1987;15(5):408–412. doi: 10.1007/BF01647755. [DOI] [PubMed] [Google Scholar]

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