Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1990 Feb 1;171(2):455–464. doi: 10.1084/jem.171.2.455

The toxicity of staphylococcal enterotoxin B in mice is mediated by T cells

PMCID: PMC2187711  PMID: 2303780

Abstract

Staphylococcal enterotoxin B (SEB) has been shown in the past to be a potent T cell stimulant in mouse or man. The toxin acts as a superantigen that is, it binds to class II MHC proteins and, as such a complex, stimulates T cells bearing particular V beta s as part of their receptors. The toxin also has several pathological effects, causing, in mice, rapid weight loss, thymus atrophy, immunosuppression, and, at high doses, death. The data in this paper show that at least one of these effects, weight loss, is T cell mediated. Staphylococcal enterotoxin-mediated weight loss is MHC dependent, and is almost absent in animals expressing MHC class II molecules, which, complexed with SEB, are poor T cell stimulants. Also, mice that lack T cell function, genetically or because of cyclosporin A treatment, lose no or less weight than controls in response to SEB. Finally, animals bred such that they express few T cells bearing V beta s with which SEB can interact lose much less weight in response to the toxin than littermate controls that have higher numbers of reactive T cells. It is therefore suggested that the pathological effects of the staphylococcal, T cell- stimulating toxins in mouse and man may be partially or wholly the consequence of massive T cell stimulation.

Full Text

The Full Text of this article is available as a PDF (683.8 KB).

Selected References

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

  1. Abe R., Foo-Phillips M., Hodes R. J. Analysis of Mlsc genetics. A novel instance of genetic redundancy. J Exp Med. 1989 Oct 1;170(4):1059–1073. doi: 10.1084/jem.170.4.1059. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Behlke M. A., Chou H. S., Huppi K., Loh D. Y. Murine T-cell receptor mutants with deletions of beta-chain variable region genes. Proc Natl Acad Sci U S A. 1986 Feb;83(3):767–771. doi: 10.1073/pnas.83.3.767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Belldegrun A., Webb D. E., Austin H. A., 3rd, Steinberg S. M., White D. E., Linehan W. M., Rosenberg S. A. Effects of interleukin-2 on renal function in patients receiving immunotherapy for advanced cancer. Ann Intern Med. 1987 Jun;106(6):817–822. doi: 10.7326/0003-4819-106-6-817. [DOI] [PubMed] [Google Scholar]
  4. Beutler B., Cerami A. Cachectin/tumor necrosis factor: an endogenous mediator of shock and inflammation. Immunol Res. 1986;5(4):281–293. doi: 10.1007/BF02935501. [DOI] [PubMed] [Google Scholar]
  5. Fischer H., Dohlsten M., Lindvall M., Sjögren H. O., Carlsson R. Binding of staphylococcal enterotoxin A to HLA-DR on B cell lines. J Immunol. 1989 May 1;142(9):3151–3157. [PubMed] [Google Scholar]
  6. Fleischer B., Schrezenmeier H. T cell stimulation by staphylococcal enterotoxins. Clonally variable response and requirement for major histocompatibility complex class II molecules on accessory or target cells. J Exp Med. 1988 May 1;167(5):1697–1707. doi: 10.1084/jem.167.5.1697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fraser J. D. High-affinity binding of staphylococcal enterotoxins A and B to HLA-DR. Nature. 1989 May 18;339(6221):221–223. doi: 10.1038/339221a0. [DOI] [PubMed] [Google Scholar]
  8. Gao E. K., Lo D., Cheney R., Kanagawa O., Sprent J. Abnormal differentiation of thymocytes in mice treated with cyclosporin A. Nature. 1988 Nov 10;336(6195):176–179. doi: 10.1038/336176a0. [DOI] [PubMed] [Google Scholar]
  9. Ikejima T., Dinarello C. A., Gill D. M., Wolff S. M. Induction of human interleukin-1 by a product of Staphylococcus aureus associated with toxic shock syndrome. J Clin Invest. 1984 May;73(5):1312–1320. doi: 10.1172/JCI111334. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Janeway C. A., Jr, Yagi J., Conrad P. J., Katz M. E., Jones B., Vroegop S., Buxser S. T-cell responses to Mls and to bacterial proteins that mimic its behavior. Immunol Rev. 1989 Feb;107:61–88. doi: 10.1111/j.1600-065x.1989.tb00003.x. [DOI] [PubMed] [Google Scholar]
  11. Julius M. H., Simpson E., Herzenberg L. A. A rapid method for the isolation of functional thymus-derived murine lymphocytes. Eur J Immunol. 1973 Oct;3(10):645–649. doi: 10.1002/eji.1830031011. [DOI] [PubMed] [Google Scholar]
  12. Jupin C., Anderson S., Damais C., Alouf J. E., Parant M. Toxic shock syndrome toxin 1 as an inducer of human tumor necrosis factors and gamma interferon. J Exp Med. 1988 Mar 1;167(3):752–761. doi: 10.1084/jem.167.3.752. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kanagawa O., Palmer E., Bill J. The T cell receptor V beta 6 domain imparts reactivity to the Mls-1a antigen. Cell Immunol. 1989 Apr 1;119(2):412–426. doi: 10.1016/0008-8749(89)90255-4. [DOI] [PubMed] [Google Scholar]
  14. Kappler J. W., Kushnir E., Marrack P. Analysis of V beta 17a expression in new mouse strains bearing the V beta a haplotype. J Exp Med. 1989 May 1;169(5):1533–1541. doi: 10.1084/jem.169.5.1533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kappler J. W., Roehm N., Marrack P. T cell tolerance by clonal elimination in the thymus. Cell. 1987 Apr 24;49(2):273–280. doi: 10.1016/0092-8674(87)90568-x. [DOI] [PubMed] [Google Scholar]
  16. Kubo R. T., Born W., Kappler J. W., Marrack P., Pigeon M. Characterization of a monoclonal antibody which detects all murine alpha beta T cell receptors. J Immunol. 1989 Apr 15;142(8):2736–2742. [PubMed] [Google Scholar]
  17. Langford M. P., Stanton G. J., Johnson H. M. Biological effects of staphylococcal enterotoxin A on human peripheral lymphocytes. Infect Immun. 1978 Oct;22(1):62–68. doi: 10.1128/iai.22.1.62-68.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Matory Y. L., Chang A. E., Lipford E. H., 3rd, Braziel R., Hyatt C. L., McDonald H. D., Rosenberg S. A. Toxicity of recombinant human interleukin-2 in rats following intravenous infusion. J Biol Response Mod. 1985 Aug;4(4):377–390. [PubMed] [Google Scholar]
  19. Melish M. E., Glasgow L. A., Turner M. D. The staphylococcal scalded-skin syndrome: isolation and partial characterization of the exfoliative toxin. J Infect Dis. 1972 Feb;125(2):129–140. doi: 10.1093/infdis/125.2.129. [DOI] [PubMed] [Google Scholar]
  20. Mollick J. A., Cook R. G., Rich R. R. Class II MHC molecules are specific receptors for staphylococcus enterotoxin A. Science. 1989 May 19;244(4906):817–820. doi: 10.1126/science.2658055. [DOI] [PubMed] [Google Scholar]
  21. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983 Dec 16;65(1-2):55–63. doi: 10.1016/0022-1759(83)90303-4. [DOI] [PubMed] [Google Scholar]
  22. Parsonnet J., Hickman R. K., Eardley D. D., Pier G. B. Induction of human interleukin-1 by toxic-shock-syndrome toxin-1. J Infect Dis. 1985 Mar;151(3):514–522. doi: 10.1093/infdis/151.3.514. [DOI] [PubMed] [Google Scholar]
  23. Peavy D. L., Adler W. H., Smith R. T. The mitogenic effects of endotoxin and staphylococcal enterotoxin B on mouse spleen cells and human peripheral lymphocytes. J Immunol. 1970 Dec;105(6):1453–1458. [PubMed] [Google Scholar]
  24. Pinto M., Torten M., Birnbaum S. C. Suppression of the in vivo humoral and cellular immune response by staphylococcal enterotoxin B (SEB). Transplantation. 1978 Jun;25(6):320–323. doi: 10.1097/00007890-197806000-00008. [DOI] [PubMed] [Google Scholar]
  25. Pullen A. M., Marrack P., Kappler J. W. Evidence that Mls-2 antigens which delete V beta 3+ T cells are controlled by multiple genes. J Immunol. 1989 May 1;142(9):3033–3037. [PubMed] [Google Scholar]
  26. Pullen A. M., Marrack P., Kappler J. W. The T-cell repertoire is heavily influenced by tolerance to polymorphic self-antigens. Nature. 1988 Oct 27;335(6193):796–801. doi: 10.1038/335796a0. [DOI] [PubMed] [Google Scholar]
  27. Rosloniec E. F., Gay D., Freed J. H. Epitopic analysis by anti-I-Ak monoclonal antibodies of I-Ak-restricted presentation of lysozyme peptides. J Immunol. 1989 Jun 15;142(12):4176–4183. [PubMed] [Google Scholar]
  28. Scheuber P. H., Denzlinger C., Wilker D., Beck G., Keppler D., Hammer D. K. Staphylococcal enterotoxin B as a nonimmunological mast cell stimulus in primates: the role of endogenous cysteinyl leukotrienes. Int Arch Allergy Appl Immunol. 1987;82(3-4):289–291. doi: 10.1159/000234209. [DOI] [PubMed] [Google Scholar]
  29. Staerz U. D., Rammensee H. G., Benedetto J. D., Bevan M. J. Characterization of a murine monoclonal antibody specific for an allotypic determinant on T cell antigen receptor. J Immunol. 1985 Jun;134(6):3994–4000. [PubMed] [Google Scholar]
  30. Tracey K. J., Beutler B., Lowry S. F., Merryweather J., Wolpe S., Milsark I. W., Hariri R. J., Fahey T. J., 3rd, Zentella A., Albert J. D. Shock and tissue injury induced by recombinant human cachectin. Science. 1986 Oct 24;234(4775):470–474. doi: 10.1126/science.3764421. [DOI] [PubMed] [Google Scholar]
  31. White J., Herman A., Pullen A. M., Kubo R., Kappler J. W., Marrack P. The V beta-specific superantigen staphylococcal enterotoxin B: stimulation of mature T cells and clonal deletion in neonatal mice. Cell. 1989 Jan 13;56(1):27–35. doi: 10.1016/0092-8674(89)90980-x. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES