Intranasal administration of one alpha gliadin can downregulate the immuneresponse to whole gliadin in mice

Citation
F. Maurano et al., Intranasal administration of one alpha gliadin can downregulate the immuneresponse to whole gliadin in mice, SC J IMMUN, 53(3), 2001, pp. 290-295
Citations number
23
Categorie Soggetti
Immunology
Journal title
SCANDINAVIAN JOURNAL OF IMMUNOLOGY
ISSN journal
03009475 → ACNP
Volume
53
Issue
3
Year of publication
2001
Pages
290 - 295
Database
ISI
SICI code
0300-9475(200103)53:3<290:IAOOAG>2.0.ZU;2-T
Abstract
The mucosal lesion present in coeliac disease is an immune-mediated injury triggered by gliadin and restricted by a particular assortment of major his tocompatibility complex genes. In view of this, an immunomodulatory approac h that induces tolerance to this antigen appears to be a possible alternati ve to a strict gluten-free diet in treating coeliac disease. We have shown that intranasal administration of multiple doses of whole gliadin is requir ed to specifically inhibit T helper 1-like T-cell reactivity in BALB/c mice immunized parenterally with whole gliadin. However, T-cell activation to m ultiple antigens, as a consequence of the chemical complexity shown by the antigen gliadin, could hamper efforts to identify single component(s) usefu l for tolerance induction. In this study, gliadin fractions were purified a nd administered intranasally to study their ability to induce tolerance to whole gliadin in our animal model. We found that the alpha fraction was par ticularly effective in downregulating both the in vitro gliadin-specific T- cell proliferation and interferon-gamma production to whole gliadin. In par ticular, a purified alpha -gliadin was able to suppress the immune response to the entire gliadin mixture. These results demonstrate how an immune res ponse to a complex antigen may be controlled by treatment with a purified c omponent and specifically indicate alpha -gliadin to be a good candidate fo r further identification of short peptides to be used as tolerogens in this model.