1. Blockage of T-cell costimulation inhibits T-cell action in celiac disease.
- Author
-
Maiuri L, Auricchio S, Coletta S, De Marco G, Picarelli A, Di Tola M, Quaratino S, and Londei M
- Subjects
- Abatacept, Antigens, CD immunology, Antigens, Differentiation immunology, Biopsy, CD40 Antigens immunology, CTLA-4 Antigen, Celiac Disease pathology, Cells, Cultured, DNA Fragmentation, Duodenum, Humans, Interferon-gamma biosynthesis, Interleukin-2 biosynthesis, Intestinal Mucosa pathology, Lymphocyte Activation, T-Lymphocytes pathology, Celiac Disease immunology, Gliadin immunology, Immunoconjugates, Intestinal Mucosa immunology, T-Lymphocytes immunology
- Abstract
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.
- Published
- 1998
- Full Text
- View/download PDF