Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1988 Apr 1;167(4):1341–1349. doi: 10.1084/jem.167.4.1341

Evidence that activated mucosal T cells play a role in the pathogenesis of enteropathy in human small intestine

PMCID: PMC2188906  PMID: 2965735

Abstract

T cells in explants of human fetal small intestine in organ culture were stimulated in situ with PWM or anti-CD3 antibody to test the hypothesis that activated T cells produce enteropathy in human small intestine. T cell activation was measured by the appearance of CD25+ cells in the lamina propria of the explants and IL-2 production into the organ culture supernatant. We have previously shown that the number of T cells in human fetal gut increased between 14 and 22 wk gestation. Accordingly, after the addition of PWM to cultured explants of fetal intestine the number of CD25+ cells in the lamina propria and the amounts of IL-2 secreted into the organ culture supernatant increased with the age of the explanted tissue. The addition of PWM also produced an age-related enteropathy, most noticeably crypt epithelial cell hyperplasia and villous atrophy, with relatively minor changes in 14-17- wk-old intestine but severe tissue damage in 18-22-wk-old fetal intestine. These enteropathic effects were also produced when mucosal T cells were activated with anti-CD3 mAb. Cyclosporin A completely inhibited the PWM-induced development of CD25+ cells and related tissue damage. These experiments show that activated T cells in human small intestine produce enteropathy. The model provides a new system with which to dissect the mechanisms of T cell-mediated intestinal damage.

Full Text

The Full Text of this article is available as a PDF (576.9 KB).

Selected References

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

  1. Autrup H., Barrett L. A., Jackson F. E., Jesudason M. L., Stoner G., Phelps P., Trump B. F., Harris C. C. Explant culture of human colon. Gastroenterology. 1978 Jun;74(6):1248–1257. [PubMed] [Google Scholar]
  2. Baker P. E., Gillis S., Smith K. A. Monoclonal cytolytic T-cell lines. J Exp Med. 1979 Jan 1;149(1):273–278. doi: 10.1084/jem.149.1.273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Elliott J. F., Lin Y., Mizel S. B., Bleackley R. C., Harnish D. G., Paetkau V. Induction of interleukin 2 messenger RNA inhibited by cyclosporin A. Science. 1984 Dec 21;226(4681):1439–1441. doi: 10.1126/science.6334364. [DOI] [PubMed] [Google Scholar]
  4. Ferguson A., Carswell F. Precipitins to dietary proteins in serum and upper intestinal secretions of coeliac children. Br Med J. 1972 Jan 8;1(5792):75–77. doi: 10.1136/bmj.1.5792.75. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Ferguson A., MacDonald T. T. Effects of local delayed hypersensitivity on the small intestine. Ciba Found Symp. 1977 Apr 26;(46):305–327. doi: 10.1002/9780470720288.ch15. [DOI] [PubMed] [Google Scholar]
  6. Granelli-Piperno A., Inaba K., Steinman R. M. Stimulation of lymphokine release from T lymphoblasts. Requirement for mRNA synthesis and inhibition by cyclosporin A. J Exp Med. 1984 Dec 1;160(6):1792–1802. doi: 10.1084/jem.160.6.1792. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. MacDonald T. T., Ferguson A. Hypersensitivity reactions in the small intestine. 2. Effects of allograft rejection on mucosal architecture and lymphoid cell infiltrate. Gut. 1976 Feb;17(2):81–91. doi: 10.1136/gut.17.2.81. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. MacDonald T. T., Ferguson A. Hypersensitivity reactions in the small intestine. III. The effects of allograft rejection and of graft-versus-host disease on epithelial cell kinetics. Cell Tissue Kinet. 1977 Jul;10(4):301–312. [PubMed] [Google Scholar]
  9. Ménard D., Arsenault P. Explant culture of human fetal small intestine. Gastroenterology. 1985 Mar;88(3):691–700. doi: 10.1016/0016-5085(85)90139-8. [DOI] [PubMed] [Google Scholar]
  10. Shiner M., Ballard J. Antigen-antibody reactions in jejunal mucosa in childhood coeliac disease after gluten challenge. Lancet. 1972 Jun 3;1(7762):1202–1205. doi: 10.1016/s0140-6736(72)90924-5. [DOI] [PubMed] [Google Scholar]
  11. Spencer J., Dillon S. B., Isaacson P. G., MacDonald T. T. T cell subclasses in fetal human ileum. Clin Exp Immunol. 1986 Sep;65(3):553–558. [PMC free article] [PubMed] [Google Scholar]
  12. Spencer J., MacDonald T. T., Finn T., Isaacson P. G. The development of gut associated lymphoid tissue in the terminal ileum of fetal human intestine. Clin Exp Immunol. 1986 Jun;64(3):536–543. [PMC free article] [PubMed] [Google Scholar]
  13. Wood G. S., Warner N. L., Warnke R. A. Anti-Leu-3/T4 antibodies react with cells of monocyte/macrophage and Langerhans lineage. J Immunol. 1983 Jul;131(1):212–216. [PubMed] [Google Scholar]

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

RESOURCES