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

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.