Summary
A proportion of epithelial lymphocytes in various mammalian species is characterised by cells containing cytoplasmic granules. We have studied the total number of granular lymphocytes within surface and crypt epithelium of jejunal mucosae (per 104 µm2 muscularis mucosae) from six groups of subjects, comprising (i) young healthy volunteers (ii) family relatives of known coeliac patients, patients with gastrointestinal disorders associated with either (iii) normal or (iv) “flat” mucosae, and groups of (v) untreated and (vi) treated patients with coeliac disease. There was no difference in the absolute number of gEL between the three control groups with normal mucosal architecture, the proportion of granular to total EL per unit of tissue varying between 30–40% . In untreated coeliac mucosae, there was a significantly increased population of gEL, compared with the same control groups (p<0.001): the ratio of granular to total EL approximated 65%, and did not differ from flat-control mucosae in which the proportion of gEL was 55%. On withdrawal of gluten, the absolute number of gEL fell significantly in comparison with the untreated coeliac group (p< 0.05). To further evaluate the effect of gluten challenge, granular lymphocytes were monitored during a five-day period in groups of treated coeliac patients orally challenged with increasing doses (500–3000 mg) of a peptic-tryptic digest of gluten. A significant rise in the absolute number of granular lymphocytes occurred at 12 h, but without any deterioration in mucosal architecture.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Arnaud-Battandier FA, Bundy BM, O'Neill M, Bienenstock J, Nelson DL (1978) Cytotoxic activities of gut mucosal lymphoid cells in guinea pigs. J Immunol 121:1059–1065
Bland CE, Rosenthal KL, Pluznik DH, Dennert G, Hengartner H, Bienenstock J, Metcalfe DD (1986) Glycosaminoglycan profiles in cloned granulated lymphocytes with natural killer function and in cultured mast cells: their potential use as biochemical markers. J Immunol 132:1937–42
Borland A, Mowat A, Parrott DMV (1983) Augmentation of intestinal and peripheral natural killer cell activity during the graft-versus-host reaction in mice. Transplantation 36:513–9
Cerf-Bensussan N, Guy-Grand D, Griscelli C (1985) Intraepithelial lymphocytes of human gut: isolation, characterisation and study of natural killer activity. Gut 26:81–88
Cerf-Bensussan N, Schneeberger EE, Bhan AK (1983) Immunohistologic and immunoelectron microscopic characterisation of the mucosal lymphocytes of human small intestine by the use of monoclonal antibodies. J Immunol 130:2615–2622
Collan Y (1972) Characteristics of non-epithelial cells in the epithelium of normal rat ileum. Scand J Gastroenterology (Suppl) 18:7
Ernst PB, Befus AD, Bienenstock J (1985) Leukocytes in the intestinal epithelium: an unusual immunological compartment. Immunol Today 6:50–55
Ferguson A (1977) Intraepithelial lymphocytes of the small intestine. Gut 18:921–937
Ferguson A (1987) Models of immunologically-driven small intestinal damage. In: Marsh MN (ed) The Immunopathology of the Small Intestine. Wiley, Chichester, pp 225–52
Flores AF, Winter HS, Bhan AK (1982) In vitro model to assess immunoregulatory T lymphocyte populations in gluten-sensitive enteropathy. Gastroenterology 82:A1058
Frazer AC, Fletcher RF, Ross CAC, Shaw B, Sammons HC (1959) Gluten-induced enteropathy. The effect of partially-digested gluten. Lancet 2:252–55
Gibson PR, Down EL, Selby WS, Strickland RG, Jewell DP (1984) Natural killer cells and spontaneous cell-mediated cytotoxicity in the human intestine. Clin Exp Immunol 56:438–44
Greenwood JH, Austin LL, Dobbins WO (1983) In vitro characterisation of human intestinal intraepithelial lymphocytes. Gastroenterology 85:1023–1035
Guy-Grand D, Vassalli P (1986) Gut injury in mouse graft-versus-host reaction: study of its occurrence and mechanisms. J Clin Invest 77:1584–1595
Landazuri MO, Lopez-Botet M, Timonen T, Ortaldo JR, Herberman RB (1981) Human large granular lymphocytes: spontaneous and interferon-boosted NK activity against adherent and non-adherent cell lines. J Immunol 127:1380–1383
Leigh RJ, Marsh MN, Crowe P, Kelly C, Garner V, Gordon D (1985) Studies of intestinal lymphoid tissue. IX-Dose-dependent, gluten-induced lymphoid infiltration of coeliac jejunal epithelium. Scand J Gastroenterol 20:715–9
Marsh MN (1975) Studies of intestinal lymphoid tissue. I - Electron microscopic evidence of “blast-transformation” in epithelial lymphocytes of mouse small intestinal mucosa. Gut 16:665–674
Marsh MN (1982) Studies of intestinal lymphoid tissue. IV - The predictive value of raised mitotic indices among jejunal epithelial lymphocytes in the diagnosis of gluten-sensitive enteropathy. J Clin Pathol 35:517–525
Marsh MN (1985) Functional and structural aspects of the epithelial lymphocyte, with implications for coeliac disease and tropical sprue. Scand J Gastroenterology (Suppl) 114:55–75
Marsh MN, Haeney MR (1983) Studies of intestinal lymphoid tissue. VI - Proliferative response of small intestinal epithelial lymphocytes distinguishes gluten- from non-gluten-induced enteropathy. J Clin Pathol 36:149–160
Mowat A McI (1987) The cellular basis of gastrointestinal immunity. In: Marsh MN (ed) The Immunopathology of the Small Intestine. Wiley, Chichester, pp 41–72
Mowat A McI, Borland A, Parrott DMV (1986) Hypersensitivity reactions in the small intestine. VII - Induction of the intestinal phase of murine graft-versus-host reaction by Lyt 2− T cells activated by I-A alloantigens. Transplantation 41:192–8
Mowat A, Tait RC, Mackenzie S, Davies MDJ, Parrott DMV (1983) Analysis of natural killer effector and suppressor activity by intraepithelial lymphocytes from mouse small intestine. Clin Exp Immunol 52:191–8
Parrott DMV, Tait C, MacKenzie S, Mowat A (1982) Analysis of the effector functions of different populations of mucosal lymphocytes. Ann N Y Acad Sci 409:307–20
Ritchie AW, James K, Micklem HS (1983) The distribution and possible significance of cells identified in human lymphoid tissues by the monoclonal antibody HNK-1. Clin Exp Immunol 51:439–47
Rubin CE, Brandborg L, Phelps P (1960) Studies of celiac disease. I. The apparent, identical and specific nature of the duodenal and proximal jejunal lesion in coeliac disease and idiopathic steatorrhoea. Gastroenterology 38:28–49
Rudzik O, Bienenstock J (1979) Isolation and characterstics of gut mucosal lymphocytes. Lab Invest 30:260–266
Selby WS, Janossy G, Bofill M, Jewell DP (1983) Lymphocyte subpopulations in the human small intestine. The findings in normal mucosa and in the mucosa of patients with adult coeliac disease. Clin Exp Immunol 52:219–228
Selby WS, Janossy G, Goldstein G, Jewell DP (1981a) T lymphocyte subsets in human intestinal mucosa: the distribution and relationship to MHC-determined antigens. Clin Exp Immunol 44:453–8
Selby WS, Janossy G, Jewell DP (1981b) Immunohistological characterisation of intraepithelial lymphocytes of the human gastrointestinal tract. Gut 22:169–176
Tagliabue A, Befus AD, Clark DA, Bienentock J (1982) Characteristics of natural killer cells in the murine intestinal epithelium and lamina propria. J Exp Med 155:1785–96
Tagliabue A, Luini W, Soldateschi D, Boraschi D (1981) Natural killer activity of gut mucosal lymphoid cells in mice. Eur J Immunol 11:919–22
Timonen T, Ortaldo JR, Heberman RB (1981) Characteristics of human large granular lymphocytes and relationship to natural killer and K cells. J Exp Med 153:569–582
Toner PG, Ferguson A (1971) Intraepithelial cells in the human intestinal mucosa. J Ultrastr Res 34:329–344
Author information
Authors and Affiliations
Additional information
Supported by the Medical Research Council, Great Britain
Rights and permissions
About this article
Cite this article
Marsh, M.N., Leigh, R.J., Loft, D.E. et al. Studies of intestinal lymphoid tissue. Vichows Archiv A Pathol Anat 412, 365–370 (1988). https://doi.org/10.1007/BF00750263
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00750263