IL-15 Drives the Specific Migration of CD94+ and TCR-γδ+ Intraepithelial Lymphocytes in Organ Cultures of Treated Celiac Patients

Maiuri, Luigi; Ciacci, Carolina; Vacca, Loredana; Ricciardelli, Ida; Auhcchio, Salvatore; Quaratino, Sonia; Londei, Marco
January 2001
American Journal of Gastroenterology;Jan2001, Vol. 96 Issue 1, p150
Academic Journal
OBJECTIVES: Celiac disease (CD) is an under-diagnosed but extremely frequent disease, triggered by the ingestion of gliadin. The pathogenic mechanisms of CD are still poorly understood, but intraepithelial lymphocytes are considered to have a key role. We intended to define the subsets of T lymphocytes migrating upon gliadin challenge in organ cultures of treated celiac patients and establish the type of factor(s) driving such an infiltration. METHODS: Duodenum biopsies from 10 treated celiacs and 7 controls were cultured in vitro with/without gliadin digest (1 mg/ml) or interleukin (IL)-15 (10 ng/ml). In 7 treated celiacs IL-7, lL-4, and lL-2 were similarly tested, Intraepithelial CD3, CDS, TCR-γδ, and CD94 were detected by immunohistochemistry and numbered per mm epithelium. RESULTS: TL-15 but not IL-7, IL-4, or IL-2 induced intra-epithelial increase of CD3+ and CD8+ cells in celiac and control intestine (p < 0.001 vs cultures with medium). IL-15 induced increases in the number of intraepithelial TCR-γδ+ and CD94+ cells only in celiacs (p < 0.001). IL-7 was also effective in increasing intraepithelial TCR-γδ+ (but not CD94+) cells in celiac biopsies (p < 0.001), Gliadin induced intraepithelial migration 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 might have a key role in modulating and driving intraepithelial infiltration and ultimately in the pathogenesis of CD.


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