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

¹ Department of Paediatrics and European Laboratory for the Investigation of Food-Induced Diseases, University Federico II, Naples, Italy
² Institute of Food, Science, and Technology, CNR Avellino, Italy
³ San Raffaele Telethon Institute of Gene Therapy (HSR-TIGET), San Raffaele Scientific Institute, Milan, Italy
⁴ Gastroenterology and Endoscopy Unit Hospital, "San Giuseppe Moscati", Avellino, Italy

Correspondence to:
Correspondence to:
Professor R Troncone
Department of Paediatrics, University Federico II, Via Pansini, No 5, 80131 Naples, Italy; troncone{at}unina.it

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 (IFN-) 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-.

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- 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.

Abbreviations: CD, coeliac disease; IL-10, interleukin 10; rhIL-10, human recombinant IL-10; NCE, non-coeliac enteropathy; RT-PCR, reverse transcription-polymerase chain reaction; TCL, T cell lines; IFN-, interferon ; Tr1 cells, type 1 T regulatory cells; TGF-ß, transforming growth factor ß; LPT, lamina propria T cells; IELs, intraepithelial lymphocytes; PT, peptic-tryptic; mAb, monoclonal antibody; PBS, phosphate buffered saline; tTG, tissue transglutaminase; PBMCs, peripheral blood mononuclear cells; SFC, spot forming cells

Keywords: interleukin 10; coeliac disease; immune suppression; organ culture; gliadin specific T cell lines

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