Gut 54:46-53 doi:10.1136/gut.2003.023150
  • Coeliac disease

Recombinant human interleukin 10 suppresses gliadin dependent T cell activation in ex vivo cultured coeliac intestinal mucosa

  1. V M Salvati1,
  2. G Mazzarella2,
  3. C Gianfrani2,
  4. M K Levings3,*,
  5. R Stefanile2,
  6. B De Giulio2,
  7. G Iaquinto4,
  8. N Giardullo4,
  9. S Auricchio1,
  10. M G Roncarolo3,
  11. R Troncone1
  1. 1Department of Paediatrics and European Laboratory for the Investigation of Food-Induced Diseases, University Federico II, Naples, Italy
  2. 2Institute of Food, Science, and Technology, CNR Avellino, Italy
  3. 3San Raffaele Telethon Institute of Gene Therapy (HSR-TIGET), San Raffaele Scientific Institute, Milan, Italy
  4. 4Gastroenterology and Endoscopy Unit Hospital, “San Giuseppe Moscati”, Avellino, Italy
  1. Correspondence to:
    Professor R Troncone
    Department of Paediatrics, University Federico II, Via Pansini, No 5, 80131 Naples, Italy;
  • Accepted 4 May 2004
  • Revised 26 March 2004


Background: Enteropathy in coeliac disease (CD) is sustained by a gliadin specific Th1 response. Interleukin (IL)-10 can downregulate Th1 immune responses.

Aim: We investigated the ability of recombinant human (rh) IL-10 to suppress gliadin induced Th1 response.

Patients and methods: IL-10 RNA transcripts were analysed by competitive reverse transcription-polymerase chain reaction in duodenal biopsies from untreated and treated CD patients, non-coeliac enteropathies (NCE), and controls. CD biopsies were cultured with a peptic-tryptic digest of gliadin with or without rhIL-10. The proportion of CD80+ and CD25+ cells in the lamina propria, epithelial expression of Fas, intraepithelial infiltration of CD3+ cells, as well as cytokine synthesis (interferon γ (IFN-γ) and IL-2) were measured. Short term T cell lines (TCLs) obtained from treated CD biopsies cultured with gliadin with or without rhIL-10 were analysed by ELISPOT for gliadin specific production of IFN-γ.

Results: In untreated CD and NCE, IL-10 RNA transcripts were significantly upregulated. In ex vivo organ cultures, rhIL-10 downregulated gliadin induced cytokine synthesis, inhibited intraepithelial migration of CD3+ cells, and reduced the proportion of lamina propria CD25+ and CD80+ cells whereas it did not interfere with epithelial Fas expression. In short term TCLs, rhIL-10 abrogated the IFN-γ response to gliadin.

Conclusions: rhIL-10 suppresses gliadin specific T cell activation. It may interfere with the antigen presenting capacity of lamina propria mononuclear cells as it reduces the expression of CD80. Interestingly, rhIL-10 also induces a long term hyporesponsiveness of gliadin specific mucosal T cells. These results offer new perspectives for therapeutic strategies in coeliac patients based on immune modulation by IL-10.


  • * Present address: Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada