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

• Published in: Gut Vol. 54; no. 1; pp. 46 - 53
• Main Authors: Salvati, V M, Mazzarella, G, Gianfrani, C, Levings, M K, Stefanile, R, De Giulio, B, Iaquinto, G, Giardullo, N, Auricchio, S, Roncarolo, M G, Troncone, R
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and British Society of Gastroenterology 01.01.2005; BMJ; BMJ Publishing Group LTD; Copyright 2005 by Gut
• Subjects: Adolescent; Adult; Antigen presentation; Biological and medical sciences; Celiac disease; Celiac Disease - diet therapy; Celiac Disease - immunology; Cell Line; Child; Child, Preschool; Coeliac Disease; Cytokines; Disease; Endoscopy; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression Regulation - immunology; Gliadin - immunology; gliadin specific T cell lines; human recombinant IL-10; Humans; IELs; IFN-γ; IL-10; immune suppression; Immune Tolerance; Infant; Inflammatory bowel disease; interferon γ; Interferon-gamma - biosynthesis; Interferon-gamma - genetics; interleukin 10; Interleukin-10 - biosynthesis; Interleukin-10 - genetics; Interleukin-10 - immunology; Intestinal Mucosa - immunology; intraepithelial lymphocytes; lamina propria T cells; LPT; Lymphocyte Activation - immunology; Lymphocytes; mAb; Medical sciences; Middle Aged; monoclonal antibody; NCE; non-coeliac enteropathy; organ culture; Organ Culture Techniques; Other diseases. Semiology; PBMCs; PBS; peptic-tryptic; peripheral blood mononuclear cells; phosphate buffered saline; Recombinant Proteins - immunology; Reverse Transcriptase Polymerase Chain Reaction - methods; reverse transcription-polymerase chain reaction; rhIL-10; RNA polymerase; RNA, Messenger - genetics; Rodents; RT-PCR; SFC; Small intestine; spot forming cells; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Studies; T cell lines; T-Lymphocyte Subsets - immunology; TCL; TGF-β; Th1 Cells - immunology; tissue transglutaminase; Tr1 cells; transforming growth factor β; tTG; type 1 T regulatory cells; Cell culture; Mucosa; Check; Th1 lymphocyte; Activation; Coeliac disease; Small intestine; Prevention; Messenger RNA; Ex vivo; Immunological investigation; Intestinal malabsorption; Gliadin; T-Lymphocyte; Intestinal disease; Reverse transcription polymerase chain reaction; Ability; Human; Immune response; Duodenum; Digestive system; Cytokine; Gut; Method; In vivo; Symptomatology; Treatment; Biopsy; Interleukin 10; Digestive diseases
• ISSN: 0017-5749; 1468-3288; 1458-3288
• DOI: 10.1136/gut.2003.023150

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.