BACKGROUND & AIMS: Celiac disease is an exemplary model of T cell-mediated pathology. Therefore, therapeutic approaches that target T cells may successfully control this disease. CTLA-4 immunoglobulin (CTLA-4Ig) can inhibit T-cell activation by blocking the engagement of CD28. We took advantage of this tool to define the pathogenic role of gliadin-specific T cells in the induction of celiac disease. METHODS: Duodenal biopsy specimens from 7 treated celiac patients were challenged in vitro with gliadin and CTLA-4Ig or CD40-Ig. After 24 hours, the biopsy specimens were analyzed for the presence of characteristic modifications induced by gliadin challenge. RESULTS: CTLA-4Ig down-regulated the expression of CD25, intercellular adhesion molecule 1, interleukin 2, and interferon gamma (stained lamina propria mononuclear cells/mm2; P < 0.05) induced by gliadin challenge, caused apoptosis of gliadin-specific T cells (apoptotic T cells/mm2; P < 0.05), and inhibited the production of antiendomysial antibody (P < 0.01). However, it did not control intraepithelial T-cell migration (P = NS) and Fas expression by enterocytes. Conversely, CD40-Ig only controlled production of antiendomysial antibody. CONCLUSIONS: In an organ culture model, CTLA-4Ig controls many but not all of the immunologic features of celiac disease.
BACKGROUND & AIMS:Celiac disease is an exemplary model of T cell-mediated pathology. Therefore, therapeutic approaches that target T cells may successfully control this disease. CTLA-4 immunoglobulin (CTLA-4Ig) can inhibit T-cell activation by blocking the engagement of CD28. We took advantage of this tool to define the pathogenic role of gliadin-specific T cells in the induction of celiac disease. METHODS: Duodenal biopsy specimens from 7 treated celiac patients were challenged in vitro with gliadin and CTLA-4Ig or CD40-Ig. After 24 hours, the biopsy specimens were analyzed for the presence of characteristic modifications induced by gliadin challenge. RESULTS: CTLA-4Ig down-regulated the expression of CD25, intercellular adhesion molecule 1, interleukin 2, and interferon gamma (stained lamina propria mononuclear cells/mm2; P < 0.05) induced by gliadin challenge, caused apoptosis of gliadin-specific T cells (apoptotic T cells/mm2; P < 0.05), and inhibited the production of antiendomysial antibody (P < 0.01). However, it did not control intraepithelial T-cell migration (P = NS) and Fas expression by enterocytes. Conversely, CD40-Ig only controlled production of antiendomysial antibody. CONCLUSIONS: In an organ culture model, CTLA-4Ig controls many but not all of the immunologic features of celiac disease.
Authors: G Mazzarella; M Maglio; F Paparo; G Nardone; R Stefanile; L Greco; Y van de Wal; Y Kooy; F Koning; S Auricchio; R Troncone Journal: Gut Date: 2003-01 Impact factor: 23.059
Authors: Giuseppe Mazzarella; Thomas T MacDonald; Virginia M Salvati; Peter Mulligan; Luigi Pasquale; Rosita Stefanile; Paolo Lionetti; Salvatore Auricchio; Francesco Pallone; Riccardo Troncone; Giovanni Monteleone Journal: Am J Pathol Date: 2003-06 Impact factor: 4.307
Authors: V M Salvati; G Mazzarella; C Gianfrani; M K Levings; R Stefanile; B De Giulio; G Iaquinto; N Giardullo; S Auricchio; M G Roncarolo; R Troncone Journal: Gut Date: 2005-01 Impact factor: 23.059
Authors: L Maiuri; C Ciacci; V Raia; L Vacca; I Ricciardelli; F Raimondi; S Auricchio; S Quaratino; M Londei Journal: Gut Date: 2001-03 Impact factor: 23.059
Authors: B Jabri; N P de Serre; C Cellier; K Evans; C Gache; C Carvalho; J F Mougenot; M Allez; R Jian; P Desreumaux; J F Colombel; C Matuchansky; H Cugnenc; M Lopez-Botet; E Vivier; A Moretta; A I Roberts; E C Ebert; D Guy-Grand; N Brousse; J Schmitz; N Cerf-Bensussan Journal: Gastroenterology Date: 2000-05 Impact factor: 22.682