IL-15 drives the specific migration of CD94+and TCR-gamma delta+ intraepithelial lymphocytes in organ cultures of treated celiac patients

OBJECTIVES: Celiac disease (CD) is an under-diagnosed but extremely frequen t disease, triggered by the ingestion of gliadin. The pathogenic mechanisms of CD are still poorly understood, but intraepithelial lymphocytes are con sidered to have a key role. We intended to define the subsets of T lymphocy tes migrating upon gliadin challenge in organ cultures of treated celiac pa tients and establish the type of factor(s) driving such an infiltration. METHODS: Duodenum biopsies from 10 treated celiacs and 7 controls were cult ured in vitro with/without gliadin digest (1 mg/ml) or interleukin (IL)-15 (10 ng/ml). In 7 treated celiacs IL-7, IL-4, and IL-2 were similarly tested . Intraepithelial CD3, CD8, TCR-gamma delta, and CD94 were detected by immu nohistochemistry and numbered per mm epithelium. RESULTS: IL-15 but not IL-7, IL-4, or IL-2 induced intraepithelial increase of CD3+ and CD8+ cells in celiac and control intestine (p < 0.001 vs cultu res with medium). IL-15 induced increases in the number of intraepithelial TCR-<gamma>delta+ and CD94+ cells only in celiacs (p < 0.001). IL-7 was als o effective in increasing intraepithelial TCR-<gamma>delta+ (but not CD94+) cells in celiac biopsies (p < 0.001). Gliadin induced intraepithelial migr ation of CD3+, CD8+ (p < 0.001), and CD94+ (p < 0.05) cells in celiacs, but not in controls. CONCLUSIONS: The results we describe in this report indicate that IL-15 mig ht have a key role in modulating and driving intraepithelial infiltration a nd ultimately in the pathogenesis of CD. (Am J Gastroenterol 2001;96:150-15 6. (C) 2001 by Am. Coll. of Gastroenterology).