Skip to main content
NCBI home page
Gut logoLink to Gut
. 1983 Aug;24(8):692–701. doi: 10.1136/gut.24.8.692

Immunoregulatory function of human intestinal mucosa lymphoid cells: evidence for enhanced suppressor cell activity in inflammatory bowel disease.

C Fiocchi, K R Youngman, R G Farmer
PMCID: PMC1420224  PMID: 6223862

Abstract

Abnormalities in immune regulation at the gut level may be relevant to the pathogenesis of inflammatory bowel disease, but little is known about the immunoregulatory properties of intestinal mononuclear cells. Therefore, we wished to see if lymphoid cells derived from the lamina propria of surgically resected bowel specimens have any modulatory effect upon the immune response of peripheral blood mononuclear cells from patients with ulcerative colitis or Crohn's disease. When autologous peripheral blood and intestinal lamina propria lymphoid cells were mixed at different ratios and cultured in the presence of phytohaemagglutinin, we were able to show that intestinal mononuclear cells had the capacity to modify the mitogenic response of the cultured cells. These intestinal immunoregulatory cells, when obtained from mucosa affected by inflammatory bowel disease, express a significantly enhanced suppressor cell activity as compared with those from non-inflamed control mucosa. Such suppressor cell activity varies with cell concentration and requires cell proliferation, but it is independent of anatomical origin (small vs large bowel), type of inflammatory bowel disease (ulcerative colitis vs Crohn's disease) or immunosuppressive therapy. These findings point to an important functional difference between inflammatory bowel disease and control intestinal mucosa mononuclear cells. The enhanced suppressor activity of lamina propria mononuclear cells may be associated with impairment of cell-mediated immunity at the gut level. This may be related to the pathogenesis of inflammatory bowel disease by leading to defective intestinal immune regulatory events, which may not be detectable at the peripheral level.

Full text

PDF
692

Selected References

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

  1. Bird A. G., Britton S. No evidence for decreased lymphocyte reactivity in Crohn's disease. Gastroenterology. 1974 Nov;67(5):926–932. [PubMed] [Google Scholar]
  2. Bland P. W., Richens E. R., Britton D. C., Lloyd J. V. Isolation and purification of human large bowel mucosal lymphoid cells: effect of separation technique on functional characteristics. Gut. 1979 Dec;20(12):1037–1046. doi: 10.1136/gut.20.12.1037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bloom B. R. Interferons and the immune system. Nature. 1980 Apr 17;284(5757):593–595. doi: 10.1038/284593a0. [DOI] [PubMed] [Google Scholar]
  4. Bookman M. A., Bull D. M. Characteristics of isolated intestinal mucosal lymphoid cells in inflammatory bowel disease. Gastroenterology. 1979 Sep;77(3):503–510. [PubMed] [Google Scholar]
  5. Bull D. M., Bookman M. A. Isolation and functional characterization of human intestinal mucosal lymphoid cells. J Clin Invest. 1977 May;59(5):966–974. doi: 10.1172/JCI108719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Chiba M., Shorter R. G., Thayer W. R., Bartnik W., ReMine S. K-Cell activity in lamina proprial lymphocytes from the human colon. Dig Dis Sci. 1979 Nov;24(11):817–822. doi: 10.1007/BF01324895. [DOI] [PubMed] [Google Scholar]
  8. Chin W., Hay J. B. A comparison of lymphocyte migration through intestinal lymph nodes, subcutaneous lymph nodes, and chronic inflammatory sites of sheep. Gastroenterology. 1980 Dec;79(6):1231–1242. [PubMed] [Google Scholar]
  9. Coovadia H. M., MacKay I. R., d'Apice A. J. Suppressor cells assayed by three different methods in patients with chronic active hepatitis and systemic lupus erythematosus. Clin Immunol Immunopathol. 1981 Feb;18(2):268–275. doi: 10.1016/0090-1229(81)90033-7. [DOI] [PubMed] [Google Scholar]
  10. Douglas A. P., Weetman A. P., Haggith J. W. The distribution and enteric loss of 51Cr-labelled lymphocytes in normal subjects and in patients with coeliac disease and other disorders of the small intestine. Digestion. 1976;14(1):29–43. doi: 10.1159/000197797. [DOI] [PubMed] [Google Scholar]
  11. Ellner J. J., Olds G. R., Kamel R., Osman G. S., el-Kholy A., Mahmoud A. A. Suppression splenic T lymphocytes in human hepatosplenic Schistosomiasis mansoni. J Immunol. 1980 Jul;125(1):308–312. [PubMed] [Google Scholar]
  12. Elson C. O., Graeff A. S., James S. P., Strober W. Covert suppressor T cells in Crohn's disease. Gastroenterology. 1981 Jun;80(6):1513–1521. [PubMed] [Google Scholar]
  13. 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]
  14. Farrant J., Knight S. C. Help and suppression by lymphoid cells as a function of cellular concentration. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3507–3510. doi: 10.1073/pnas.76.7.3507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Fiocchi C., Battisto J. R., Farmer R. G. Gut mucosal lymphocytes in inflammatory bowel disease: isolation and preliminary functional characterization. Dig Dis Sci. 1979 Sep;24(9):705–717. doi: 10.1007/BF01314469. [DOI] [PubMed] [Google Scholar]
  16. Fiocchi C., Battisto J. R., Farmer R. G. Studies on isolated gut mucosal lymphocytes in inflammatory bowel disease. Detection of activated T cells and enhanced proliferation to Staphylococcus aureus and lipopolysaccharides. Dig Dis Sci. 1981 Aug;26(8):728–736. doi: 10.1007/BF01316863. [DOI] [PubMed] [Google Scholar]
  17. Gitnick G. L., Arthur M. H., Shibata I. Cultivation of viral agents from Crohn's disease. A new sensitive system. Lancet. 1976 Jul 31;2(7979):215–217. doi: 10.1016/s0140-6736(76)91022-9. [DOI] [PubMed] [Google Scholar]
  18. Gitnick G. L., Rosen V. J., Arthur M. H., Hertweck S. A. Evidence for the isolation of a new virus from ulcerative colitis patients. Comparison with virus derived from Crohn's disease. Dig Dis Sci. 1979 Aug;24(8):609–619. doi: 10.1007/BF01333705. [DOI] [PubMed] [Google Scholar]
  19. Glick M. E., Falchuk Z. M. Dinitrochlorobenzene-induced colitis in the guinea-pig: studies of colonic lamina propria lymphocytes. Gut. 1981 Feb;22(2):120–125. doi: 10.1136/gut.22.2.120. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Goodacre R. L., Bienenstock J. Reduced suppressor cell activity in intestinal lymphocytes from patients with Crohn's disease. Gastroenterology. 1982 Apr;82(4):653–658. [PubMed] [Google Scholar]
  21. Goodwin J. S., Webb D. R. Regulation of the immune response by prostaglandins. Clin Immunol Immunopathol. 1980 Jan;15(1):106–122. doi: 10.1016/0090-1229(80)90024-0. [DOI] [PubMed] [Google Scholar]
  22. Heron I., Berg K., Cantell K. Regulatory effect of interferon on T cells in vitro. J Immunol. 1976 Oct;117(4):1370–1373. [PubMed] [Google Scholar]
  23. Hillinger S. M., Herzig G. P. Impaired cell-mediated immunity in Hodgkin's disease mediated by suppressor lymphocytes and monocytes. J Clin Invest. 1978 Jun;61(6):1620–1627. doi: 10.1172/JCI109082. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Hodgson H. J., Wands J. R., Isselbacher K. J. Decreased suppressor cell activity in inflammatory bowel disease. Clin Exp Immunol. 1978 Jun;32(3):451–458. [PMC free article] [PubMed] [Google Scholar]
  25. Janossy G., Tidman N., Selby W. S., Thomas J. A., Granger S., Kung P. C., Goldstein G. Human T lymphocytes of inducer and suppressor type occupy different microenvironments. Nature. 1980 Nov 6;288(5786):81–84. doi: 10.1038/288081a0. [DOI] [PubMed] [Google Scholar]
  26. Kung P., Goldstein G., Reinherz E. L., Schlossman S. F. Monoclonal antibodies defining distinctive human T cell surface antigens. Science. 1979 Oct 19;206(4416):347–349. doi: 10.1126/science.314668. [DOI] [PubMed] [Google Scholar]
  27. Kurnick J. T., Bell C., Grey H. M. PHA-induced activation of suppressor cells in normal human peripheral blood lymphocytes. Scand J Immunol. 1976;5(6-7):771–778. doi: 10.1111/j.1365-3083.1976.tb03026.x. [DOI] [PubMed] [Google Scholar]
  28. Lobo P. I., Spencer C. E. Inhibition of humoral and cell-mediated immune responses in man by distinct suppressor cell systems. J Clin Invest. 1979 Jun;63(6):1157–1163. doi: 10.1172/JCI109409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. MacDermott R. P., Bragdon M. J., Jenkins K. M., Franklin G. O., Shedlofsky S., Kodner I. J. Human intestinal mononuclear cells. II. Demonstration of a naturally occurring subclass of T cells which respond in the allogeneic mixed leukocyte reaction but do not effect cell-mediated lympholysis. Gastroenterology. 1981 Apr;80(4):748–757. [PubMed] [Google Scholar]
  30. 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]
  31. Rampton D. S., Sladen G. E., Youlten L. J. Rectal mucosal prostaglandin E2 release and its relation to disease activity, electrical potential difference, and treatment in ulcerative colitis. Gut. 1980 Jul;21(7):591–596. doi: 10.1136/gut.21.7.591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. ReMine S. G., Bartnik W., Bahn R. C., Shorter R. G. Further characterization of lymphocytes from human colonic lamina propria: identification of TG cells. Clin Exp Immunol. 1981 Nov;46(2):294–300. [PMC free article] [PubMed] [Google Scholar]
  33. Reinherz E. L., Parkman R., Rappeport J., Rosen F. S., Schlossman S. F. Aberrations of suppressor T cells in human graft-versus-host disease. N Engl J Med. 1979 May 10;300(19):1061–1068. doi: 10.1056/NEJM197905103001901. [DOI] [PubMed] [Google Scholar]
  34. Reinherz E. L., Schlossman S. F. Current concepts in immunology: Regulation of the immune response--inducer and suppressor T-lymphocyte subsets in human beings. N Engl J Med. 1980 Aug 14;303(7):370–373. doi: 10.1056/NEJM198008143030704. [DOI] [PubMed] [Google Scholar]
  35. Rose M. L., Parrott D. M., Bruce R. G. Migration of lymphoblasts to the small intestine. II. Divergent migration of mesenteric and peripheral immunoblasts to sites of inflammation in the mouse. Cell Immunol. 1976 Nov;27(1):36–46. doi: 10.1016/0008-8749(76)90151-9. [DOI] [PubMed] [Google Scholar]
  36. Sachar D. B., Taub R. N., Brown S. M., Present D. H., Korelitz B. I., Janowitz H. D. Imparied lymphocyte responsiveness in inflammatory bowel disease. Gastroenterology. 1973 Feb;64(2):203–209. [PubMed] [Google Scholar]
  37. Stobo J. D., Paul S., Van Scoy R. E., Hermans P. E. Suppressor thymus-derived lymphocytes in fungal infection. J Clin Invest. 1976 Feb;57(2):319–328. doi: 10.1172/JCI108283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Tosato G., Magrath I., Koski I., Dooley N., Blaese M. Activation of suppressor T cells during Epstein-Barr-virus-induced infectious mononucleosis. N Engl J Med. 1979 Nov 22;301(21):1133–1137. doi: 10.1056/NEJM197911223012101. [DOI] [PubMed] [Google Scholar]
  39. Victorino R. M., Hodgson H. J. Alteration in T lymphocyte subpopulations in inflammatory bowel disease. Clin Exp Immunol. 1980 Jul;41(1):156–165. [PMC free article] [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES