Blockage of T-cell costimulation inhibits T-cell action in celiac disease

Background and 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-4lg) 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-4lg or CD40-lg. After 24 hours, the biopsy specimens were analyzed for the presence of characteristic modifications induced by gliadin challenge. Results: CTLA-4lg 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-lg only controlled production of antiendomysial antibody. Conclusions: In an organ culture model, CTLA-4lg controls many but not all of the immunologic features of celiac disease.