IL-15 drives the specific migration of CD94+ and TCR-gammadelta+ intraepithelial lymphocytes in organ cultures of treated celiac patients.
OBJECTIVE
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-gammadelta, 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- gammadelta+ and CD94+ cells only in celiacs (p < 0.001). IL-7 was also effective in increasing intraepithelial TCR-gammadelta+ (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.
Maiuri
L
L
Department of Pediatrics, University Federico II Naples, Italy.
Ciacci
C
C
Vacca
L
L
Ricciardelli
I
I
Auricchio
S
S
Quaratino
S
S
Londei
M
M
D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000276:immunology*; D001707:Biopsy, Needle; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D002446:Celiac Disease / Q000178:diet therapy / Q000276:immunology* / Q000473:pathology; D002465:Cell Movement / Q000276:immunology*; D046508:Culture Techniques; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019409:Interleukin-15 / Q000276:immunology* / Q000494:pharmacology; D037181:Lectins, C-Type; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology*; D008875:Middle Aged; D051920:NK Cell Lectin-Like Receptor Subfamily D; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000187:drug effects / Q000276:immunology*; D012016:Reference Values; D012680:Sensitivity and Specificity
D015703:Antigens, CD; D017252:CD3 Complex; D016827:CD8 Antigens; D019409:Interleukin-15; C497869:KLRD1 protein, human; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D051920:NK Cell Lectin-Like Receptor Subfamily D; D016692:Receptors, Antigen, T-Cell, gamma-delta