Majority of Gliadin-specific T-cell Clones from Celiac Small Intestinal Mucosa Produce Interferon-gamma and Interleukin-4

Overview

Journal Dig Dis Sci

Specialty Gastroenterology

Date 1998 Mar 21

PMID 9508518

Citations 17

Authors

R Troncone

C Gianfrani

G Mazzarella

L Greco

J Guardiola

S Auricchio

P De Berardinis

Affiliations

Soon will be listed here.

Abstract

An abnormal mucosal cell-mediated immune response plays a fundamental role in the pathogenesis of celiac disease. To characterize locally infiltrating T cells, gliadin-specific T-cell clones were isolated from two treated celiac patients. Mucosal biopsies were cultured in vitro for 24 hr with a peptic-tryptic digest (PT) of gliadin. T-cell clones (TCC) were then isolated by limiting dilution. The production of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) was evaluated by ELISA in culture supernatants obtained after a short incubation with anti-CD3 and PMA, or with antigen. Twenty-two TCC were specific for gliadin and/or PT. All were CD3+, CD4+, CD8-, TCR alphabeta+. In one such clone the PT-specific response was inhibited by an anti-DQ, but not by an anti-DR antibody. Of the five gliadin-specific TCC examined, four produced IL-4 and high levels of IFN-gamma; the remaining one initially produced only IL-4, but subsequently also IFN-gamma. All clones obtained from the celiac mucosa, including the gliadin-specific ones, produced high levels of IFN-gamma, in most cases with IL-4. This cytokine profile could explain most of the immunological features of the celiac mucosa.

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References

Maiuri L, Picarelli A, Boirivant M, COLETTA S, Mazzilli M, De Vincenzi M . Definition of the initial immunologic modifications upon in vitro gliadin challenge in the small intestine of celiac patients. Gastroenterology. 1996; 110(5):1368-78. DOI: 10.1053/gast.1996.v110.pm8613040. View

Nilsen E, Gjertsen H, Jensen K, Brandtzaeg P, Lundin K . Gluten activation of peripheral blood T cells induces a Th0-like cytokine pattern in both coeliac patients and controls. Clin Exp Immunol. 1996; 103(2):295-303. PMC: 2200356. DOI: 10.1046/j.1365-2249.1996.d01-611.x. View

Halstensen T, Scott H, Fausa O, Brandtzaeg P . Gluten stimulation of coeliac mucosa in vitro induces activation (CD25) of lamina propria CD4+ T cells and macrophages but no crypt-cell hyperplasia. Scand J Immunol. 1993; 38(6):581-90. DOI: 10.1111/j.1365-3083.1993.tb03245.x. View

Quaranta V, Pellegrino M, Ferrone S . Serologic and immunochemical characterization of the specificity of four monoclonal antibodies to distinct antigenic determinants expressed on subpopulations of human Ia-like antigens. J Immunol. 1981; 126(2):548-52. View

Ciclitira P, Nelufer J, Ellis H, Evans D . The effect of gluten on HLA-DR in the small intestinal epithelium of patients with coeliac disease. Clin Exp Immunol. 1986; 63(1):101-4. PMC: 1577323. View

Troncone R, Greco L, Auricchio S . Gluten-sensitive enteropathy. Pediatr Clin North Am. 1996; 43(2):355-73. DOI: 10.1016/s0031-3955(05)70410-7. View

Fais S, Maiuri L, Pallone F, De Vincenzi M, De Ritis G, Troncone R . Gliadin induced changes in the expression of MHC-class II antigens by human small intestinal epithelium. Organ culture studies with coeliac disease mucosa. Gut. 1992; 33(4):472-5. PMC: 1374061. DOI: 10.1136/gut.33.4.472. View

Auricchio S, De Ritis G, De Vincenzi M, Occorsio P, Silano V . Effects of gliadin-derived peptides from bread and durum wheats on small intestine cultures from rat fetus and coeliac children. Pediatr Res. 1982; 16(12):1004-10. DOI: 10.1203/00006450-198212000-00006. View

Kontakou M, Przemioslo R, Sturgess R, Limb G, Ellis H, Day P . Cytokine mRNA expression in the mucosa of treated coeliac patients after wheat peptide challenge. Gut. 1995; 37(1):52-7. PMC: 1382768. DOI: 10.1136/gut.37.1.52. View

10.

Maiuri L, Troncone R, Mayer M, COLETTA S, Picarelli A, De Vincenzi M . In vitro activities of A-gliadin-related synthetic peptides: damaging effect on the atrophic coeliac mucosa and activation of mucosal immune response in the treated coeliac mucosa. Scand J Gastroenterol. 1996; 31(3):247-53. DOI: 10.3109/00365529609004874. View

11.

Lundin K, Scott H, Hansen T, Paulsen G, Halstensen T, Fausa O . Gliadin-specific, HLA-DQ(alpha 1*0501,beta 1*0201) restricted T cells isolated from the small intestinal mucosa of celiac disease patients. J Exp Med. 1993; 178(1):187-96. PMC: 2191064. DOI: 10.1084/jem.178.1.187. View

12.

Halstensen T, Brandtzaeg P . Activated T lymphocytes in the celiac lesion: non-proliferative activation (CD25) of CD4+ alpha/beta cells in the lamina propria but proliferation (Ki-67) of alpha/beta and gamma/delta cells in the epithelium. Eur J Immunol. 1993; 23(2):505-10. DOI: 10.1002/eji.1830230231. View

13.

Breese E, Kumar P, Farthing M, MacDonald T . Interleukin-2 and interferon-gamma producing cells in the lamina propria in celiac disease. Dig Dis Sci. 1994; 39(10):2243. DOI: 10.1007/BF02090378. View

14.

Marsh M . Gluten, major histocompatibility complex, and the small intestine. A molecular and immunobiologic approach to the spectrum of gluten sensitivity ('celiac sprue'). Gastroenterology. 1992; 102(1):330-54. View

15.

Al-Dawoud A, Nakshabendi I, Foulis A, Mowat A . Immunohistochemical analysis of mucosal gamma-interferon production in coeliac disease. Gut. 1992; 33(11):1482-6. PMC: 1379532. DOI: 10.1136/gut.33.11.1482. View

16.

Kontakou M, Sturgess R, Przemioslo R, Limb G, Nelufer J, Ciclitira P . Detection of interferon gamma mRNA in the mucosa of patients with coeliac disease by in situ hybridisation. Gut. 1994; 35(8):1037-41. PMC: 1375051. DOI: 10.1136/gut.35.8.1037. View

17.

Mowat A, Widmer M . A role for IL-4 in immunologically mediated enteropathy. Clin Exp Immunol. 1995; 99(1):65-9. PMC: 1534147. DOI: 10.1111/j.1365-2249.1995.tb03473.x. View

18.

Lundin K, Scott H, Fausa O, Thorsby E, Sollid L . T cells from the small intestinal mucosa of a DR4, DQ7/DR4, DQ8 celiac disease patient preferentially recognize gliadin when presented by DQ8. Hum Immunol. 1994; 41(4):285-91. DOI: 10.1016/0198-8859(94)90047-7. View

19.

Kontakou M, Przemioslo R, Sturgess R, Limb A, Ciclitira P . Expression of tumour necrosis factor-alpha, interleukin-6, and interleukin-2 mRNA in the jejunum of patients with coeliac disease. Scand J Gastroenterol. 1995; 30(5):456-63. DOI: 10.3109/00365529509093307. View

20.

Przemioslo R, Lundin K, Sollid L, Nelufer J, Ciclitira P . Histological changes in small bowel mucosa induced by gliadin sensitive T lymphocytes can be blocked by anti-interferon gamma antibody. Gut. 1995; 36(6):874-9. PMC: 1382625. DOI: 10.1136/gut.36.6.874. View