Skip to main content
SpringerLink
Log in

Crohn's disease

New concepts of pathogenesis and current approaches to treatment

  • Review Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

One theory of the pathogenesis of Crohn's disease is that rather than being caused by a unique environmental agent, it is the result of an abnormal immune response in the gastrointestinal tract. Recent studies indicate that Crohn's disease in its early stages is frequently associated with the presence of circulating antigen-non-specific suppressor T cells. Such T cells are also found in experimental inflammation caused byChlamydia organisms in the gastrointestinal tract of nonhuman primates. Taken together, these data suggest that the suppressor T cells are markers of an underlying and persistent, antigen-specific immune response to an as yet unidentified antigen or set of antigens. We postulate that this underlying antigen-specific response is the result of a primary immunoregulatory abnormality involving an imbalance between the effects of antigen-specific helper and suppressor T cells which recognize a common antigen or antigens present in the mucosal environment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Schmitz-Moorman P, Becker H: Histological studies on the formal pathogenesis of the epithelial granuloma and Crohn's disease.In Developments in Gastroenterology, Vol. 1, Recent Advances in Crohn's Disease. AS Pena, IT Weterman, CC Booth, W Strober (eds). The Hague, Martinus Nijhoff, 1981, pp 76–79

    Google Scholar 

  2. Bookman MA, Bull DM: Characteristics of isolated intestinal mucosal lymphoid cells in inflammatory bowel disease. Gastroenterology 77:503–510, 1979

    Google Scholar 

  3. Baklien K, Brandtzaeg P: Comparative mapping of the focal distribution of immunoglobulin-containing cells in ulcerative colitis and Crohn's disease of the colon. Clin Exp Immunol 22:197–209, 1975

    Google Scholar 

  4. James SP, Fiocchi C, Graeff AS, Strober W: Immunoregulatory function of lamina propria T cells in Crohn's disease. Gastroenterology 88:1143–1150, 1985

    Google Scholar 

  5. Saverymuttu SH, Peters AM, Lavender JP, Pepys MB, Hodgson HJF, Chadwick VS: Quantitative fecal indium 111-labelled leukocyte excretion in the assessment of disease in Crohn's disease. Gastroenterology 85:1333–1339, 1983

    Google Scholar 

  6. Sharon P, Stenson WF: Enhanced synthesis of leukotriene B4 by colonic mucosa in inflammatory bowel disease. Gastroenterology 86:454–460, 1984

    Google Scholar 

  7. Strober W, Richman LK, Elson CO: The regulation of gastroentertinal immune responses. Immunol Today 2:156–161, 1981

    Google Scholar 

  8. Richman LK, Chiller JM, Brown WR, Hanson DG, Vaz NM: Enterically induced immunologic tolerance. I. Induction of suppressor T lymphocytes by intragastric administration of soluble proteins. J Immunol 121:2429–2434, 1978

    Google Scholar 

  9. Gautam SC, Battisto JR: Orally induced tolerance generates an efficiently acting suppressor T cell and an acceptor T cell that together down-regulate contact sensitivity. J Immunol 135:2975–2983, 1985

    Google Scholar 

  10. Kagnoff MF: Effects of antigen feeding on intestinal and specific immune response. III. Antigen specific serum-mediated suppression of humoral antibody responses after antigen feeding. Cell Immunol 40:186–203, 1978

    Google Scholar 

  11. Richman LK: Immunologic unresponsiveness after enteric administration of protein antigens.In Immunology of Breast Milk. PL Ogra, D Dayton (eds). New York, Raven Press, 1979; pp 49–59

    Google Scholar 

  12. Reynolds JD, Morris B: The effect of antigen on the development of Peyer's patches in sheep. J Immunol 14:1–6, 1984

    Google Scholar 

  13. Richman LK, Graeff AS, Yarchoan R, Strober W: Simultaneous induction of antigen-specific IgA helper T cells and IgG suppressor T cells in the murine Peyer's patch after protein feeding. J Immunol 126:2079–2083, 1981

    Google Scholar 

  14. Walker WA, Bloch KJ: Intestinal uptake of macromolecules:In vitro andin vivo studies. Ann NY Acad Sci 409:593–602, 1983

    Google Scholar 

  15. Socken DJ, Simms ES, Nagy BR, Fisher MM, Underdown BJ: Secretory component-dependent hepatic transport of IgA antibody-antigen complexes. J Immunol 127:316–319, 1981

    Google Scholar 

  16. Michalek SM, Kiyono H, Wannemuehler MJ, Mosteller LM, McGhee JR: Lipopolysaccharide (LPS) regulation of the immune response: LPS influence on oral tolerance induction. J Immunol 128:1992–1998, 1982

    Google Scholar 

  17. Elson CO, Graeff AS, James SP, Strober W: Covert suppressor T cells in Crohn's disease. Gastroenterology 80: 1513–1521, 1981

    Google Scholar 

  18. Elson CO, James SP, Graeff AS, Berendson RA, Strober W: Hypogammaglobulinemia due to abnormal suppressor T cell activity in Crohn's disease. Gastroenterology 86:569–576, 1984

    Google Scholar 

  19. James SP, Nekers LM, Graeff AS, Cossman J, Balch CM, Strober W: Suppression of immunoglobulin synthesis by lymphocyte subpopulations in patients with Crohn's disease. Gastroenterology 86:1510–1518, 1984

    Google Scholar 

  20. Fiocchi C, Battisto JR, Farmer RG: Gut mucosal lymphocytes in Crohn's disease. Isolation and preliminary characterization. Dig Dis Sci 24:705–717, 1979

    Google Scholar 

  21. James JP, Fiocchi C, Graeff AS, Strober W: Immunoregulatory function of lamina propria T cells in Crohn's disease. Gastroenterology 88:1143–1150, 1985

    Google Scholar 

  22. Crohn BB, Ginzburg L, Oppenheimer GD: Regional ileitis: A pathological and clinical entity. JAMA 99:1323–1329, 1932

    Google Scholar 

  23. Kirsner JB, Shorter RG: Recent developments in “nonspecific” inflammatory bowel disease. N Engl J Med 306:775–784, 837–848, 1982

    Google Scholar 

  24. Chiodini RJ, Van Kruiningen HJ, Thayer WR, Coutu JA, Merkal RS: Mycobacterial spheroblasts isolated from patients with Crohn's disease. Gastroenterology 88:1348–1352, 1985

    Google Scholar 

  25. Vantrappen G, Agg HO, Ponette E, Geboes K, Bertrand PH:Yersinia enteritis and enterocolitis: Gastroenterological aspects. Gastroenterology 72:220–227, 1977

    Google Scholar 

  26. Quinn TC, Goodell SE, Mkrtichian E, et al:Chlamydia trachomatis proctitis. N Engl J Med 305:195–200, 1981

    Google Scholar 

  27. Levin I, Romano S, Steinberg M, Welsh RA: Lymphogranuloma venereum: Rectal stricture and carcinoma. Dis Colon Rectum 7:129–134, 1964

    Google Scholar 

  28. Levin JS, Smith PD, Brugge WR: Chronic proctitis in male homosexuals due to lymphogranuloma venereum. Gastroenterology 79:563–565, 1980

    Google Scholar 

  29. Crohn BB, Yarnis H. Regional ileitis. New York, Grune & Stratton, 1958

    Google Scholar 

  30. Rodaniche EC, Kirsner JB, Palmer WL: The relationship between lymphogranuloma venereum and regional enteritis: An etiologic study of 4 cases with negative results. Gastroenterology 1:687–689, 1943

    Google Scholar 

  31. Tomenius J, Larre E, Lindgren I, Blumenthal B, Lindewall G: Positive Frei tests in 7 cases of morbus Crohn (regional ileitis). Gastroenterologica 99:368–373, 1963

    Google Scholar 

  32. Schuller JL, Picket-van Ulsen J, Veeken IVD, Michel MF, Stolz E: Antibodies againstChlamydia of lymphogranulomavenereum type in Crohn's disease. Lancet 1:19–20, 1979

    Google Scholar 

  33. Mardh P-A, Ursing B, Sandgren E: Lack of evidence for an association between infection withChlamydia trachomatis and Crohn's disease, as indicated by micro-immunofluorescence antibody tests. Acta Pathol Microbiol Scand 88:57–59, 1980

    Google Scholar 

  34. Taylor-Robinson D, O'Morain CA, Thomas BJ, Levi AJ: Low frequency of chlaymdial antibodies in patients with Crohn's disease and ulcerative colitis. Lancet 1:1162–1163, 1979

    Google Scholar 

  35. Swarbrick ET, Price HL, Kingham JGC, Blackshaw AJ, Griffiths PD:Chlamydia, cytomegalovirus, and Yersinia in inflammatory bowel disease. Lancet 2:11–12, 1979

    Google Scholar 

  36. Elliott PR, Forset T, Darougar S, Treharne JD Lennard-Jones JE:Chlamydia and inflammatory bowel disease. Gut 22:25–27, 1981

    Google Scholar 

  37. Quinn TC, Taylor HI, Schacter J: Experimental proctitis by rectal infection withChlamydia trachomatis in non-human primates. J Infect Dis 154:833–841, 1986

    Google Scholar 

  38. Klotz SA, Drut DJ, Tam MR, Reed KH: Hemorrhagic proctitis due to lymphogranuloma venereum serogroups L2: Diagnosis by fluorescent monoclonal antibody. N Engl J Med 308:1563–1565, 1983

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Mucosal Immunity Section, Laboratory of Clinical Investigation, NIAID, National Institute of Health, Building 10, Room 11 N-250, 20892, Bethesda, Maryland

    S. P. James,  W. Strober, T. C. Quinn & S. H. Danovitch

  2. Infectious Disease Division, Department of Internal Medicine, The Johns Hopkins University School of Medicine, Balitmore, Maryland

    S. P. James,  W. Strober, T. C. Quinn & S. H. Danovitch

Authors
  1. S. P. James
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. W. Strober
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T. C. Quinn
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. H. Danovitch
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

James, S.P., Strober, W., Quinn, T.C. et al. Crohn's disease. Digest Dis Sci 32, 1297–1310 (1987). https://doi.org/10.1007/BF01296381

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01296381

Key Words

Search

Navigation