CONICET | Buscador de Institutos y Recursos Humanos

Objectives: To screen for CD30 expression on duodenal T cells as an activation marker in celiac disease, and to investigate the regulation of CD30 by interleukin (IL)-15 in peripheral blood lymphocytes (PBL). Materials/methods: During diagnostic gastro-duodenoscopy multiple biopsy specimens and concomitant blood samples were obtained from patients with untreated celiac disease (Cel, n=7) and healthy controls (Co, n=5). Intraepithelial and lamina propria lymphocytes (IEL and LPL) were isolated at baseline, and after 3-hour incubation of biopsies with 100 ug/ml of crude gliadin. Triple immunofluorescence staining with anti CD25 PE, -CD3 PerCP and -CD30 FITC and flow cytometry analysis was performed. At baseline, comparisons were performed among Cel and Co. Also, patients and Co were individually assessed at baseline and after gliadin challenge. PBL were incubated with 1 ug/ml of anti-CD3 for 3 days. T cell blasts were reseeded, cultured for additional 3 days with 50 ng/ml of recombinant human IL-15 and similarly evaluated by triple immunostaining followed by flow cytometry analysis. Unpaired Student t- test was used in this study, p <0.05 was considered statistically significant. Results: A similar frequency of CD3+ cells among isolated CD3+IEL and CD3+LPL was found at baseline (Cel vs.Co, p=ns). In both Cel and Co individually assessed, gliadin did not influence CD30 expression on IEL. However, gliadin induced the up regulation of CD30 on a subpopulation of CD3+ LPL in 4/6 Cel but not in controls. Resting peripheral T cells did not express CD30+ antigen. Incubation with anti-CD3 induced its expression on a subpopulation of CD3+CD25+ cells from both Co and Cel. After addition of IL-15, CD30 expression was significantly increased in both groups (p<0.05, anti-CD3+IL-15 vs. anti-CD3). Conclusions: CD30 is marker of a persistently activated subpopulation of duodenal T cells in child. We observed the up regulation of CD30 on a subpopulation of LPL in Cel and also that IL-15 potentiates CD30 up regulation on T cell peripheral blasts. It is known that mucosal cells produce IL-15 after challenging with gliadin. Consequently, endogen IL-15 elicited by treatment of biopsy cultures with gliadin might have induced the CD30 up regulation observed on LPL. After triggering by CD30, co stimulatory signals for the activation/proliferation of an activated subpopulation of CD30+ LPL might be probably involved in CD pathogenesis.

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