Maiuri, Luigi, Ciacci, Carolina, Vacca, Loredana, Ricciardelli, Ida, Auricchio, Salvatore, Quaratino, Sonia and Londei, Marco
IL-15 drives the specific migration of CD94+ and TCR-??+ intraepithelial lymphocytes in organ cultures of treated celiac patients
American Journal of Gastroenterology, 96, (1), . (doi:10.1111/j.1572-0241.2001.03437.x).
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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, IL-4, and IL-2 were similarly tested. Intraepithelial CD3, CD8, TCR-??, and CD94 were detected by immunohistochemistry 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 cultures with medium). IL-15 induced increases in the number of intraepithelial TCR-??+ and CD94+ cells only in celiacs (p< 0.001). IL-7 was also effective in increasing intraepithelial TCR-??+ (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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