Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1990 Oct;86(4):1255–1260. doi: 10.1172/JCI114832

Lack of induction of suppressor T cells by intestinal epithelial cells from patients with inflammatory bowel disease.

L Mayer 1, D Eisenhardt 1
PMCID: PMC296856  PMID: 2145321

Abstract

The mechanisms underlying the chronic unrelenting inflammatory response seen in inflammatory bowel disease (IBD) are poorly understood. We have recently proposed a novel role for the normal intestinal enterocyte, that of antigen presenting cell. However, in contrast to conventional antigen presenting cells, normal enterocytes appear to selectively activate CD8+ antigen nonspecific suppressor T cells. To determine whether failure of this process may be occurring in inflammatory bowel disease, freshly isolated enterocytes from small and large bowel from normal patients, patients with Crohn's disease, ulcerative colitis, and inflammatory (diverticulitis, ischemic colitis, and gold induced colitis) controls were co-cultured with allogeneic T cells in a modified mixed lymphocyte reaction. In contrast to normal enterocytes, 42/42 Crohn's and 35/38 ulcerative colitis-derived epithelial cells stimulated CD4+ T cells, whereas 65/66 and 9/9 normal and inflammatory control enterocytes, respectively, stimulated CD8+ T cells (as previously described), suggesting that the results seen were not just a reflection of underlying inflammation. Furthermore, IBD enterocytes from both histologically involved and uninvolved tissue were similar in their ability to selectively activate CD4+ T cells, speaking for a more global defect in epithelial cells in IBD. Finally, activated T cells from IBD epithelial cell-stimulated mixed lymphocyte cultures displayed potent T helper activity in an antigen nonspecific fashion. Taken together, these data suggest that there may be an intrinsic defect in epithelial cells from patients with IBD, resulting in the inability to normally stimulate suppressor T cells in an antigen overloaded environment.

Full text

PDF
1255

Selected References

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

  1. BROBERGER O., PERLMANN P. In vitro studies of ulcerative colitis. I. Reactions of patients' serum with human fetal colon cells in tissue cultures. J Exp Med. 1963 May 1;117:705–716. doi: 10.1084/jem.117.5.705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bland P. W., Warren L. G. Antigen presentation by epithelial cells of the rat small intestine. I. Kinetics, antigen specificity and blocking by anti-Ia antisera. Immunology. 1986 May;58(1):1–7. [PMC free article] [PubMed] [Google Scholar]
  3. Bland P. W., Warren L. G. Antigen presentation by epithelial cells of the rat small intestine. II. Selective induction of suppressor T cells. Immunology. 1986 May;58(1):9–14. [PMC free article] [PubMed] [Google Scholar]
  4. Cerf-Bensussan N., Quaroni A., Kurnick J. T., Bhan A. K. Intraepithelial lymphocytes modulate Ia expression by intestinal epithelial cells. J Immunol. 1984 May;132(5):2244–2252. [PubMed] [Google Scholar]
  5. Chiba M., Bartnik W., ReMine S. G., Thayer W. R., Shorter R. G. Human colonic intraepithelial and lamina proprial lymphocytes: cytotoxicity in vitro and the potential effects of the isolation method on their functional properties. Gut. 1981 Mar;22(3):177–186. doi: 10.1136/gut.22.3.177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Damle N. K., Engleman E. G. Immunoregulatory T cell circuits in man. Alloantigen-primed inducer T cells activate alloantigen-specific suppressor T cells in the absence of the initial antigenic stimulus. J Exp Med. 1983 Jul 1;158(1):159–173. doi: 10.1084/jem.158.1.159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Donowitz M. Arachidonic acid metabolites and their role in inflammatory bowel disease. An update requiring addition of a pathway. Gastroenterology. 1985 Feb;88(2):580–587. doi: 10.1016/0016-5085(85)90525-6. [DOI] [PubMed] [Google Scholar]
  8. Falchuk Z. M., Barnhard E., Machado I. Human colonic mononuclear cells: studies of cytotoxic function. Gut. 1981 Apr;22(4):290–294. doi: 10.1136/gut.22.4.290. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fiocchi C., Tubbs R. R., Youngman K. R. Human intestinal mucosal mononuclear cells exhibit lymphokine-activated killer cell activity. Gastroenterology. 1985 Mar;88(3):625–637. doi: 10.1016/0016-5085(85)90130-1. [DOI] [PubMed] [Google Scholar]
  10. Geboes K., Rutgeerts P., Penninckx F., Desmet V., Vantrappen G. Changes in small intestinal epithelial expression of MHC class II antigen after terminal ileal resection for Crohn's disease. Int J Colorectal Dis. 1988 Jun;3(2):102–108. doi: 10.1007/BF01645314. [DOI] [PubMed] [Google Scholar]
  11. Hirata I., Berrebi G., Austin L. L., Keren D. F., Dobbins W. O., 3rd Immunohistological characterization of intraepithelial and lamina propria lymphocytes in control ileum and colon and in inflammatory bowel disease. Dig Dis Sci. 1986 Jun;31(6):593–603. doi: 10.1007/BF01318690. [DOI] [PubMed] [Google Scholar]
  12. MacDermott R. P., Bragdon M. J., Kodner I. J., Bertovich M. J. Deficient cell-mediated cytotoxicity and hyporesponsiveness to interferon and mitogenic lectin activation by inflammatory bowel disease peripheral blood and intestinal mononuclear cells. Gastroenterology. 1986 Jan;90(1):6–11. doi: 10.1016/0016-5085(86)90067-3. [DOI] [PubMed] [Google Scholar]
  13. MacDermott R. P., Franklin G. O., Jenkins K. M., Kodner I. J., Nash G. S., Weinrieb I. J. Human intestinal mononuclear cells. I. Investigation of antibody-dependent, lectin-induced, and spontaneous cell-mediated cytotoxic capabilities. Gastroenterology. 1980 Jan;78(1):47–56. [PubMed] [Google Scholar]
  14. Mason D. W., Dallman M., Barclay A. N. Graft-versus-host disease induces expression of Ia antigen in rat epidermal cells and gut epithelium. Nature. 1981 Sep 10;293(5828):150–151. doi: 10.1038/293150a0. [DOI] [PubMed] [Google Scholar]
  15. Mayer L., Fu S. M., Cunningham-Rundles C., Kunkel H. G. Polyclonal immunoglobulin secretion in patients with common variable immunodeficiency using monoclonal B cell differentiation factors. J Clin Invest. 1984 Dec;74(6):2115–2120. doi: 10.1172/JCI111636. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mayer L., Fu S. M., Kunkel H. G. Human T cell hybridomas secreting factors for IgA-specific help, polyclonal B cell activation, and B cell proliferation. J Exp Med. 1982 Dec 1;156(6):1860–1865. doi: 10.1084/jem.156.6.1860. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Mayer L., Kwan S. P., Thompson C., Ko H. S., Chiorazzi N., Waldmann T., Rosen F. Evidence for a defect in "switch" T cells in patients with immunodeficiency and hyperimmunoglobulinemia M. N Engl J Med. 1986 Feb 13;314(7):409–413. doi: 10.1056/NEJM198602133140703. [DOI] [PubMed] [Google Scholar]
  18. Mayer L., Shlien R. Evidence for function of Ia molecules on gut epithelial cells in man. J Exp Med. 1987 Nov 1;166(5):1471–1483. doi: 10.1084/jem.166.5.1471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. PERLMANN P., BROBERGER O. In vitro studies of ulcerative colitis. II. Cytotoxic action of white blood cells from patients on human fetal colon cells. J Exp Med. 1963 May 1;117:717–733. doi: 10.1084/jem.117.5.717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Phillpotts R. J., Hermon-Taylor J., Brooke B. N. Virus isolation studies in Crohn's disease: a negative report. Gut. 1979 Dec;20(12):1057–1062. doi: 10.1136/gut.20.12.1057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Scott M. G., Nahm M. H., Macke K., Nash G. S., Bertovich M. J., MacDermott R. P. Spontaneous secretion of IgG subclasses by intestinal mononuclear cells: differences between ulcerative colitis, Crohn's disease, and controls. Clin Exp Immunol. 1986 Oct;66(1):209–215. [PMC free article] [PubMed] [Google Scholar]
  22. Selby W. S., Janossy G., Mason D. Y., Jewell D. P. Expression of HLA-DR antigens by colonic epithelium in inflammatory bowel disease. Clin Exp Immunol. 1983 Sep;53(3):614–618. [PMC free article] [PubMed] [Google Scholar]
  23. Sharon P., Stenson W. F. Enhanced synthesis of leukotriene B4 by colonic mucosa in inflammatory bowel disease. Gastroenterology. 1984 Mar;86(3):453–460. [PubMed] [Google Scholar]
  24. Shorter R. G., McGill D. B., Bahn R. C. Cytotoxicity of mononuclear cells for autologous colonic epithelial cells in colonic diseases. Gastroenterology. 1984 Jan;86(1):13–22. [PubMed] [Google Scholar]
  25. Targan S. R., Kagnoff M. F., Brogan M. D., Shanahan F. Immunologic mechanisms in intestinal diseases. Ann Intern Med. 1987 Jun;106(6):853–870. doi: 10.7326/0003-4819-106-6-853. [DOI] [PubMed] [Google Scholar]
  26. Targan S., Britvan L., Kendal R., Vimadalal S., Soll A. Isolation of spontaneous and interferon inducible natural killer like cells from human colonic mucosa: lysis of lymphoid and autologous epithelial target cells. Clin Exp Immunol. 1983 Oct;54(1):14–22. [PMC free article] [PubMed] [Google Scholar]
  27. Taylor-Robinson D., O'Morain C. A., Thomas B. J., Levi A. J. Low frequency of chlamydial antibodies in patients with Crohn's disease and ulcerative colitis. Lancet. 1979 Jun 2;1(8127):1162–1163. doi: 10.1016/s0140-6736(79)91843-9. [DOI] [PubMed] [Google Scholar]
  28. Vande Stouwe R. A., Kunkel H. G., Halper J. P., Weksler M. E. Autologous mixed lymphocyte culture reactions and generation of cytotoxic T cells. J Exp Med. 1977 Dec 1;146(6):1809–1814. doi: 10.1084/jem.146.6.1809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Veillette A., Bookman M. A., Horak E. M., Samelson L. E., Bolen J. B. Signal transduction through the CD4 receptor involves the activation of the internal membrane tyrosine-protein kinase p56lck. Nature. 1989 Mar 16;338(6212):257–259. doi: 10.1038/338257a0. [DOI] [PubMed] [Google Scholar]
  30. Wolf J. L., Bye W. A. The membranous epithelial (M) cell and the mucosal immune system. Annu Rev Med. 1984;35:95–112. doi: 10.1146/annurev.me.35.020184.000523. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES