DEFINITION OF THE INITIAL IMMUNOLOGICAL MODIFICATIONS UPON IN-VITRO GLIADIN CHALLENGE IN THE SMALL-INTESTINE OF CELIAC PATIENTS

Background & Aims: Mucosal cell-mediated immune response is considered the central event in the pathogenesis of celiac disease, In cultured intestinal explants from celiacs in remission, we have characterized t he early stages of gliadin-induced immune activation. Methods: Intesti nal biopsy specimens (15 treated celiacs and 13 controls) were culture d with gliadin or maize prolamine digests for 24 hours as well as for 1, 2, 4, 6, 8, and 12 hours in some subjects, The expression of immuno logic markers was detected by immunocytochemistry. Results: Gliadin ch allenge may initiate two parallel pathways, one of which leads to T-ce ll activation and another that precedes it, Epithelial cells over-expr ess DR molecules after 1 hour, and in a second stage T lymphocytes bec ome fully activated, Moreover, T lymphocytes migrate in the upper muco sal layers, T lymphocytes that migrate in the higher lamina propria co mpartments are mainly CD4(+) and show markers of activation; migrating intraepithelial lymphocytes are CD8(+) and do not express these marke rs, Conclusions: In vitro gliadin challenge is a suitable model to rep roduce various immunologic features of celiac lesions; these may be ca used by different pathways, The comprehension of these phenomena is es sential to clarify the distinctive pathogenic mechanisms leading to di sease and may help in defining novel therapeutical approaches.