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Gut 49:380-386 doi:10.1136/gut.49.3.380
  • Coeliac disease

Intraepithelial and lamina propria lymphocytes show distinct patterns of apoptosis whereas both populations are active in Fas based cytotoxicity in coeliac disease

  1. A Di Sabatinoa,
  2. R Ciccocioppob,
  3. S D'Alòb,
  4. R Parronib,
  5. D Millimaggib,
  6. M G Cifoneb,
  7. G R Corazzaa
  1. aGastroenterology Unit, IRCCS Policlinico S Matteo, University of Pavia, Pavia, Italy, bDepartments of Experimental and Internal Medicine, University of L'Aquila, L'Aquila, Italy
  1. Professor G R Corazza, Unità di Gastroenterologia, IRCCS Policlinico San Matteo, Piazzale Golgi 5, 27100 Pavia, Italy.gr.corazza{at}smatteo.pv.it
  • Accepted 12 February 2001

Abstract

BACKGROUND Lamina propria (LPLs) and intraepithelial (IELs) lymphocytes are markedly increased in coeliac mucosa, and are thought to play a crucial role in the generation of villous atrophy in coeliac disease (CD). However, the mechanisms by which they mediate the killing of enterocytes in this condition are still poorly characterised.

AIM We investigated Fas mediated cytotoxicity and apoptosis of both LPLs and IELs, isolated from 10 untreated coeliac patients, 10 coeliac patients on a gluten free diet, and 10 biopsied controls.

METHODS Fas and Fas ligand expression were assessed by flow cytometry and immunocytochemistry. Lymphocyte cytotoxicity against Fas expressing Jurkat cells was determined by the Jam test. The effect of the antagonist ZB4 anti-Fas antibody on apoptotic activity exerted by coeliac lymphocytes against enterocytes was analysed. Lymphocyte apoptosis was assessed by oligonucleosome ELISA.

RESULTS LPLs and IELs showed increased apoptotic activity and higher levels of Fas ligand expression in untreated CD compared with treated CD patients and controls. Enterocyte apoptosis observed after coculturing coeliac lymphocytes and enterocytes in the presence of ZB4 antibody was reduced. In active CD, LPLs manifested increased apoptosis whereas IELs showed decreased apoptosis.

CONCLUSIONS Our results support the involvement of the Fas/Fas ligand system in CD associated enterocyte apoptosis. Increased LPL apoptosis is likely to downregulate mucosal inflammation whereas decreased IEL apoptosis could be responsible for autoimmune and malignant complications of CD.

Footnotes

  • Abbreviations used in this paper:
    CD
    coeliac disease
    FasL
    Fas ligand
    IELs
    intraepithelial lymphocytes
    LPLs
    lamina propria lymphocytes
    PBS
    phosphate buffered saline
    FCS
    fetal calf serum
    TUNEL
    terminal deoxynucleotidyl transferase mediated digoxigenin-deoxyuridine triphosphate nick end labelling