Digestive Diseases and Sciences

, Volume 37, Issue 1, pp 33–39 | Cite as

Role of T lymphocytes in intestinal mucosal injury

Inflammatory changes in athymic nude rats
  • Renata D'Inca
  • Peter Ernst
  • Richard H. Hunt
  • Mary H. Perdue
Original Articles


To determine the role of T cells versus mast cells in mucosal injury, we documented structural and functional changes in the intestine of congenitally athymic nude rats during infection with the enteric parasite,Nippostrongylus brasiliensis. Studies were conducted at days 4, 7, 10, and 21 postinfection; controls were uninfected. Villus damage was indicated by morphological abnormalities at days 7, 10, and 21 and reduced activities of disaccharidase enzymes at days 10 and 21. The activity of the proliferative enzyme, thymidine kinase, was increased only at day 21, at which time the crypts were elongated. Epithelial permeability increased significantly: 5-hr recovery (in urine and blood) of the probe molecule, [51Cr]EDTA, following injection into ligated jejunal segments, was elevated at days 7 and 10. Uptake of a protein antigen, ovalbumin, from lumen to blood followed a similar pattern. No evidence of functional T cells was demonstrated. However, mucosal mast-cell activation was indicated by elevated serum levels of rat mast-cell protease II at days 7 and 10. We conclude that the absence of thymus-derived T cells does not preclude mucosal damage involving impaired barrier and digestive function. Mucosal mast cells may be involved in causing the injury in this model.

Key Words

mast cells T cells Nippostrongylus brasiliensis inflammation epithelium mucosal injury 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Modigliani R, Mary JY, Simon JF, Cortot A, Soule JC, Gendre JP, Rene E: Clinical, biological and endoscopic picture of attacks of Crohn's disease. Evolution of prednisolone. Gastroenterology 98:811–818, 1990Google Scholar
  2. 2.
    Rubin CE, Brandborg LL, Phelps PC, Taylor HC: Studies of celiac sprue. I. The apparent, identical and specific nature of the duodenal and proximal jejunal lesion in celiac disease and idiopathic steatorrhea. Gastroenterology 38:28–49, 1960Google Scholar
  3. 3.
    Kirzner B, Kelly MH, Butler DG, Gall DG, Hamilton JR: Transmissible gastroenteritis: Sodium transport and the intestinal epithelium during the course of viral enteritis. Gastroenterology 72:457–461, 1977Google Scholar
  4. 4.
    Walker-Smith JA: Food-sensitive enteropathies. Clin Gastroenterol 15:55–69, 1986Google Scholar
  5. 5.
    Hoskins LC, Winawer SJ, Broitman SA, Gottlieb LS, Zamcheck N: Clinical giardiasis and intestinal malabsorption. Gastroenterology 53:265–279, 1977Google Scholar
  6. 6.
    Symons LEA: Kinetics of the epithelial cells and morphology of villi and crypts in the jejunum of the rat infected by the nematodeNippostrongylus brasiliensis. Gastroenterology 49:158–168, 1965Google Scholar
  7. 7.
    Ferguson A, Jarrett EEE: Hypersensitivity reactions in the small intestine. I. Thymus dependence of experimental “partial villus atrophy.” Gut 16:114–117, 1975Google Scholar
  8. 8.
    Guy-Grand D, Vassalli P: Gut injury in mouse graft-versushost reaction. Study of its occurrence and mechanisms. J Clin Invest 77:1584–1595, 1986Google Scholar
  9. 9.
    Ferreira R, Forsyth LE, Richman PI, Wells C, Spencer JO, MacDonald TT: Changes in the rate of crypt epithelial cell proliferation and mucosal morphology induced by a T-cellmediated response in human small intestine. Gastroenterology 98:1255–1263, 1990Google Scholar
  10. 10.
    Perdue MH, Ramage JK, Burget D, Marshall J, Masson S: Intestinal mucosal injury is associated with mast cell activation and leukotriene generation duringNippostrongylus-induced inflammation in the rat. Dig Dis Sci 34:724–731, 1989Google Scholar
  11. 11.
    Ramage JK, Hunt RH, Perdue MH: Changes in intestinal permeability and epithelial differentiation in the rat. Gut 29:57–61, 1988Google Scholar
  12. 12.
    Ramage JK, Stanisz A, Scicchitano R, Hunt RH, Perdue MH: Effect of immunological reactions on rat intestinal epithelium. Correlation of increased permeability to chromium 51-labeled ethylenediaminetetraacetic acid and ovalbumin during acute inflammation and anaphylaxis. Gastroenterology 94:1368–1375, 1988Google Scholar
  13. 13.
    Vos JG, Kreeftenberg JG, Kruijt BC, Kruizinga W, Steerenberg P: The athymic nude rat. II. Immunological characteristics. Clin Immunol Immunopathol 15:229–237, 1980Google Scholar
  14. 14.
    Festing MFW: Athymic nude rats.In Immunologic Defects in Laboratory Animals. ME Gershwin, B Merchant (eds). New York, Plenum, 1981, pp 267–289Google Scholar
  15. 15.
    Perdue MH, Chung M, Gall DG: Effect of anaphylaxis on gut function in the rat. Gastroenterology 86:391–397, 1984Google Scholar
  16. 16.
    McMenamin CG, Gault EA, Haig DM: The effect of dexamethasone on growth and differentiation of bone marrow derived mast cellsin vitro. Immunolgy 62:29–34, 1987Google Scholar
  17. 17.
    Stanisz AM, Befus AD, Bienenstock J: Differential effect of vasoactive intestinal peptide, substance P and somatostatin on immunoglobulin synthesis and cell proliferation by lymphocytes from spleen, peyers patches, and mesenteric lymph nodes. J Immunol 136:152–156, 1986Google Scholar
  18. 18.
    Powers GD, Abbas AK, Miller RA: Frequencies of IL-2 and IL-4 secreting T cells in naive and antigen-stimulated lymphocyte populations. J Immunol 140:3352–3357, 1988Google Scholar
  19. 19.
    Manson-Smith DF, Bruce RG, Parrott DMV: Villous atrophy and expulsion of intestinalTrichinella spiralis are mediated by T cells. Cell Immunol 47:285–292, 1979Google Scholar
  20. 20.
    Woodbury RG, Miller HRP, Huntley JF, Newlands GFJ, Palliser AC, Wakelin D: Mucosal mast cells are functionally active during the spontaneous expulsion of primary intestinal nenatode infections in the rat. Nature 312:450–452, 1984Google Scholar
  21. 21.
    Miller HRP, King SJ, Gibson S, Huntley JF, Newlands GFJ, Woodbury RG: Intestinal mucosal mast cells in normal and parasitized rats.In Mast Cell Differentiation and Heterogeneity. AD Befus, JA Denburg, J Bienenstock (eds). New York, Raven Press 1986, pp 239–255Google Scholar
  22. 22.
    Perdue MH, Forstner JF, Roomi NW, Gall DG: Epithelial response to intestinal anaphylaxis in rats: goblet cell secretion and enterocyte damage. Am J Physiol 247:G532-G637, 1984Google Scholar
  23. 23.
    Freier S, Eran M, Goldstein R: The effect of immediate type gastrointestinal allergic reactions on brush border enzymes and gut morphology in the rat. Pediatr Res 19:456–459, 1985Google Scholar
  24. 24.
    Lake AM, Kagey-Sobotka A, Jakubowicz T, Lichtenstein LM: Histamine release in acute anaphylactic enteropathy of the rat. J Immunol 133:1529–1534, 1984Google Scholar
  25. 25.
    Patrick MK, Dunn IJ, Buret A, Miller HRP, Huntley JF, Gibson S, Gall DG: Mast cell protease release and mucosal ultrastructure during intestinal anaphylaxis in the rat. Gastroenterology 94:1–9, 1988Google Scholar
  26. 26.
    D'Inca R, Ramage J, Hunt RH, Perdue MH: Antigeninduced mucosal damage and restitution in the small intestine of the immunized rat. Int Arch Allergy Appl Immunol 91:270–277, 1990Google Scholar
  27. 27.
    Schwartz LB, Austen KF: Structure and function of the chemical mediators of mast cells. Prog Allergy 34:271–321, 1984Google Scholar
  28. 28.
    Gordon JR, Burd PR, Galli SJ: Mast cells as a source of multifunctional cytokines. Immunol Today 11:458–464, 1990Google Scholar
  29. 29.
    Haig DM, McKee TA, Jarrett EEE, Woodbury R, Miller HRP: Generation of mucosal mast cells is stimulatedin vitro by factors derived from stimulated T cells of helminthinfected rats. Nature 300:188–190, 1982Google Scholar
  30. 30.
    Mayerhofer G, Bazin H: Nature of the thymus-dependency of mucosal mast cells. III. Mucosal mast cells in nude mice and nude rats, and in B rats and in a child with the Di George syndrome. Int Arch Allergy Appl Immunol 64:320–331, 1981Google Scholar
  31. 31.
    Aldenborg F, Enerback L: Histamine content and mast cell numbers in tissues of normal and athymic rats. Agents Actions 17:454–459, 1985Google Scholar

Copyright information

© Plenum Publishing Corporation 1992

Authors and Affiliations

  • Renata D'Inca
    • 1
  • Peter Ernst
    • 1
  • Richard H. Hunt
    • 1
  • Mary H. Perdue
    • 1
  1. 1.Intestinal Diseases Research Unit, Department of Pathology, Faculty of Health Sciences, 3N5CMcMaster UniversityHamiltonCanada

Personalised recommendations