Abstract
Since the identification of gliadin as aetiologic factor in coeliac disease (CD), a strict gluten-free diet has become the cornerstone of the therapy. The mucosal lesion in CD represents an immunologically mediated injury triggered by gliadin and restricted by a particular assortment of MHC genes. In this context an immunomodulatory strategy inducing tolerance to this antigen appears a possible alternative treatment. Aim of this study was to explore in an animal model the intranasal, in comparison to the intravenous (iv) mute of antigen administration, to downregulate the specific immune response. Methods: Balb/c mice from a colony reared on a gluten-free diet were instilled into the nostrils, or injected iv, with a single 50 lag dose (day -7), or multiple 50 lag doses (days -7, -6, -5, -4), of native gliadin dissolved in water, before parenteral immunization by intrafootpad injections of 50 lag gliadin emulsified in complete Freund's adjuvant (day 0). The systemic specific immune response was analysed by in vitro proliferative response of popliteal lymph nodes cells at day 10. Antigliadin total IgG and IgG1 and IgG2a subclasses were assessed by ELISA in sera obtained at day 21. Results: We found that, while a single intranasal dose failed to induce tolerance, multiple intranasal doses were as effective as repeated iv doses in suppressing (p<0.001) the T cell-mediated immune response to gliadin. Titres of gliadin-specific total IgG and subclasses showed no significant differences, but a trend towards lower IgG2a levels was observed in mice receiving gliadin iv. Conclusion: Our work indicates that intranasal administration of gliadin is an immunoregulatory strategy capable to prevent specific T-mediated immune responses in mice. These findings suggest that the nasal mucosa could represent a privileged site for the reinduction of tolerance in CD, a condition possibly characterized by a defective intestinal handling of gliadin. Supported by a Telethon grant (project D60).
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