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Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1995 Mar;99(3):398–403. doi: 10.1111/j.1365-2249.1995.tb05564.x

Cytotoxic activity of V beta 8+ T cells in Crohn's disease: the role of bacterial superantigens.

M E Baca-Estrada 1, D K Wong 1, K Croitoru 1
PMCID: PMC1534200  PMID: 7882562

Abstract

In Crohn's disease, disease-related stimuli could alter the T cell receptor (TCR) repertoire. To examine the possibility that changes in function may occur in T cell subsets without obvious changes in expression of TCR, we analysed the TCR repertoire of cytotoxic T lymphocytes in Crohn's disease peripheral blood. Furthermore, we examined the effect of bacterial superantigens, staphylococcal enterotoxin B (SEB) and E (SEE) on the cytotoxic function of T cell subsets bearing different TCR V genes using MoAbs specific for CD3 and TCR V gene products in a redirected cytotoxicity assay. There was no difference between patients and controls in the cytotoxicity measured in concanavalin A (Con A)-stimulated peripheral blood mononuclear cells (PBMC) with anti-CD3 or with six of seven anti-TCR V gene MoAbs. However, the cytotoxicity of V beta 8 T cells was decreased in Crohn's disease patients. This was not due to a decrease in total or CD8+ T cells expressing V beta 8. Furthermore, in normal subjects, PBMC stimulation with SEE and SEB selectively expanded and increased the cytotoxicity of V beta 8 and V beta 12 T cells, respectively. In Crohn's disease, although SEB stimulation increased the number and cytolytic function of the V beta 12 subset, SEE stimulation failed to increase cytolytic activity of V beta 8+ T cells in spite of the expansion of V beta 8+ T cells. These results suggest that the changes in cytotoxic function observed in V beta 8 T cells in Crohn's patients may reflect previous exposure to a V beta 8-selective superantigen.

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Selected References

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  1. Abe J., Kotzin B. L., Jujo K., Melish M. E., Glode M. P., Kohsaka T., Leung D. Y. Selective expansion of T cells expressing T-cell receptor variable regions V beta 2 and V beta 8 in Kawasaki disease. Proc Natl Acad Sci U S A. 1992 May 1;89(9):4066–4070. doi: 10.1073/pnas.89.9.4066. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aisenberg J., Ebert E. C., Mayer L. T-cell activation in human intestinal mucosa: the role of superantigens. Gastroenterology. 1993 Nov;105(5):1421–1430. doi: 10.1016/0016-5085(93)90147-5. [DOI] [PubMed] [Google Scholar]
  3. Choi Y. W., Kotzin B., Herron L., Callahan J., Marrack P., Kappler J. Interaction of Staphylococcus aureus toxin "superantigens" with human T cells. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8941–8945. doi: 10.1073/pnas.86.22.8941. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Choy M. Y., Walker-Smith J. A., Williams C. B., MacDonald T. T. Differential expression of CD25 (interleukin-2 receptor) on lamina propria T cells and macrophages in the intestinal lesions in Crohn's disease and ulcerative colitis. Gut. 1990 Dec;31(12):1365–1370. doi: 10.1136/gut.31.12.1365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dayan C. M., Chu N. R., Londei M., Rapoport B., Feldmann M. T cells involved in human autoimmune disease are resistant to tolerance induction. J Immunol. 1993 Aug 1;151(3):1606–1613. [PubMed] [Google Scholar]
  6. Drake C. G., Kotzin B. L. Superantigens: biology, immunology, and potential role in disease. J Clin Immunol. 1992 May;12(3):149–162. doi: 10.1007/BF00918083. [DOI] [PubMed] [Google Scholar]
  7. Go C., Lancki D. W., Fitch F. W., Miller J. Anergized T cell clones retain their cytolytic ability. J Immunol. 1993 Jan 15;150(2):367–376. [PubMed] [Google Scholar]
  8. Grant M. D., Smaill F. M., Laurie K., Rosenthal K. L. Changes in the cytotoxic T-cell repertoire of HIV-1-infected individuals: relationship to disease progression. Viral Immunol. 1993 Spring;6(1):85–95. doi: 10.1089/vim.1993.6.85. [DOI] [PubMed] [Google Scholar]
  9. Gulwani-Akolkar B., Posnett D. N., Janson C. H., Grunewald J., Wigzell H., Akolkar P., Gregersen P. K., Silver J. T cell receptor V-segment frequencies in peripheral blood T cells correlate with human leukocyte antigen type. J Exp Med. 1991 Nov 1;174(5):1139–1146. doi: 10.1084/jem.174.5.1139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Ignatowicz L., Kappler J., Marrack P. The effects of chronic infection with a superantigen-producing virus. J Exp Med. 1992 Apr 1;175(4):917–923. doi: 10.1084/jem.175.4.917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Irwin M. J., Gascoigne N. R. Interplay between superantigens and the immune system. J Leukoc Biol. 1993 Nov;54(5):495–503. doi: 10.1002/jlb.54.5.495. [DOI] [PubMed] [Google Scholar]
  12. James S. P. Remission of Crohn's disease after human immunodeficiency virus infection. Gastroenterology. 1988 Dec;95(6):1667–1669. doi: 10.1016/s0016-5085(88)80094-5. [DOI] [PubMed] [Google Scholar]
  13. Janeway C. Immune recognition. Mls: makes a little sense. Nature. 1991 Feb 7;349(6309):459–461. doi: 10.1038/349459a0. [DOI] [PubMed] [Google Scholar]
  14. Kappler J., Kotzin B., Herron L., Gelfand E. W., Bigler R. D., Boylston A., Carrel S., Posnett D. N., Choi Y., Marrack P. V beta-specific stimulation of human T cells by staphylococcal toxins. Science. 1989 May 19;244(4906):811–813. doi: 10.1126/science.2524876. [DOI] [PubMed] [Google Scholar]
  15. Kawabe Y., Ochi A. Programmed cell death and extrathymic reduction of Vbeta8+ CD4+ T cells in mice tolerant to Staphylococcus aureus enterotoxin B. Nature. 1991 Jan 17;349(6306):245–248. doi: 10.1038/349245a0. [DOI] [PubMed] [Google Scholar]
  16. Kawabe Y., Ochi A. Selective anergy of V beta 8+,CD4+ T cells in Staphylococcus enterotoxin B-primed mice. J Exp Med. 1990 Oct 1;172(4):1065–1070. doi: 10.1084/jem.172.4.1065. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lee W. T., Vitetta E. S. Memory T cells are anergic to the superantigen staphylococcal enterotoxin B. J Exp Med. 1992 Aug 1;176(2):575–579. doi: 10.1084/jem.176.2.575. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. MacDonald H. R., Baschieri S., Lees R. K. Clonal expansion precedes anergy and death of V beta 8+ peripheral T cells responding to staphylococcal enterotoxin B in vivo. Eur J Immunol. 1991 Aug;21(8):1963–1966. doi: 10.1002/eji.1830210827. [DOI] [PubMed] [Google Scholar]
  19. Moss P. A., Rosenberg W. M., Bell J. I. The human T cell receptor in health and disease. Annu Rev Immunol. 1992;10:71–96. doi: 10.1146/annurev.iy.10.040192.000443. [DOI] [PubMed] [Google Scholar]
  20. O'Hehir R. E., Lamb J. R. Induction of specific clonal anergy in human T lymphocytes by Staphylococcus aureus enterotoxins. Proc Natl Acad Sci U S A. 1990 Nov;87(22):8884–8888. doi: 10.1073/pnas.87.22.8884. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Offner H., Buenafe A. C., Vainiene M., Celnik B., Weinberg A. D., Gold D. P., Hashim G., Vandenbark A. A. Where, when, and how to detect biased expression of disease-relevant V beta genes in rats with experimental autoimmune encephalomyelitis. J Immunol. 1993 Jul 1;151(1):506–517. [PubMed] [Google Scholar]
  22. Otten G. R., Germain R. N. Split anergy in a CD8+ T cell: receptor-dependent cytolysis in the absence of interleukin-2 production. Science. 1991 Mar 8;251(4998):1228–1231. doi: 10.1126/science.1900952. [DOI] [PubMed] [Google Scholar]
  23. Phillips J. H., Lanier L. L. Lectin-dependent and anti-CD3 induced cytotoxicity are preferentially mediated by peripheral blood cytotoxic T lymphocytes expressing Leu-7 antigen. J Immunol. 1986 Mar 1;136(5):1579–1585. [PubMed] [Google Scholar]
  24. Posnett D. N. Do superantigens play a role in autoimmunity? Semin Immunol. 1993 Feb;5(1):65–72. doi: 10.1006/smim.1993.1009. [DOI] [PubMed] [Google Scholar]
  25. Posnett D. N., Schmelkin I., Burton D. A., August A., McGrath H., Mayer L. F. T cell antigen receptor V gene usage. Increases in V beta 8+ T cells in Crohn's disease. J Clin Invest. 1990 Jun;85(6):1770–1776. doi: 10.1172/JCI114634. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Qiao L., Golling M., Autschbach F., Schürmann G., Meuer S. C. T cell receptor repertoire and mitotic responses of lamina propria T lymphocytes in inflammatory bowel disease. Clin Exp Immunol. 1994 Aug;97(2):303–308. doi: 10.1111/j.1365-2249.1994.tb06085.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rammensee H. G., Kroschewski R., Frangoulis B. Clonal anergy induced in mature V beta 6+ T lymphocytes on immunizing Mls-1b mice with Mls-1a expressing cells. Nature. 1989 Jun 15;339(6225):541–544. doi: 10.1038/339541a0. [DOI] [PubMed] [Google Scholar]
  28. Rellahan B. L., Jones L. A., Kruisbeek A. M., Fry A. M., Matis L. A. In vivo induction of anergy in peripheral V beta 8+ T cells by staphylococcal enterotoxin B. J Exp Med. 1990 Oct 1;172(4):1091–1100. doi: 10.1084/jem.172.4.1091. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Rüthlein J., Heinze G., Auer I. O. Anti-CD2 and anti-CD3 induced T cell cytotoxicity of human intraepithelial and lamina propria lymphocytes. Gut. 1992 Dec;33(12):1626–1632. doi: 10.1136/gut.33.12.1626. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Schreiber S., MacDermott R. P., Raedler A., Pinnau R., Bertovich M. J., Nash G. S. Increased activation of isolated intestinal lamina propria mononuclear cells in inflammatory bowel disease. Gastroenterology. 1991 Oct;101(4):1020–1030. doi: 10.1016/0016-5085(91)90729-5. [DOI] [PubMed] [Google Scholar]
  31. Shanahan F., Deem R., Nayersina R., Leman B., Targan S. Human mucosal T-cell cytotoxicity. Gastroenterology. 1988 Apr;94(4):960–967. doi: 10.1016/0016-5085(88)90554-9. [DOI] [PubMed] [Google Scholar]
  32. Shanahan F., Leman B., Deem R., Niederlehner A., Brogan M., Targan S. Enhanced peripheral blood T-cell cytotoxicity in inflammatory bowel disease. J Clin Immunol. 1989 Jan;9(1):55–64. doi: 10.1007/BF00917128. [DOI] [PubMed] [Google Scholar]
  33. 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]
  34. Wigzell H., Grunewald J., Tehrani M., Esin S., Mellstedt H., Osterborg A., Dersimonian H., Brenner M., Ahlberg R., Lefvert A. K. T cell V-gene usage in man in some normal and abnormal situations. Ann N Y Acad Sci. 1991 Dec 30;636:9–19. doi: 10.1111/j.1749-6632.1991.tb33433.x. [DOI] [PubMed] [Google Scholar]

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