Intranasal administration of a recombinant alpha-gliadin down-regulates the immune response to wheat gliadin in DQ8 transgenic mice.
The mucosal lesion in coeliac disease (CD) is an immune-mediated injury triggered by gliadin and associated with HLA-DQ2 and HLA-DQ8. In view of this, an approach that re-induces tolerance to this antigen should be considered as possible alternative to a strict gluten-free diet in treating CD. However, T-cell activation to multiple antigens, as a consequence of the chemical complexity shown by the antigen gliadin, could hamper the efforts to identify single component(s) useful for tolerance induction. To address this issue, a recombinant alpha-gliadin was tested in tolerance experiments in HLA-DQ8 transgenic mice. As tissue transglutaminase (tTG) treatment of gliadin, previously reported to enhance its stimulatory activity in CD, did not increase its immunogenicity when parenterally administered in these mice, untreated gliadin was used as immunogen. A decrease in systemic T cell responses to the recombinant alpha-gliadin was found after nasal administration of antigen, reflected by lymphocytes proliferation assay. Interestingly, while the immunisation protocol induced transcription of both Th1 (IFN-gamma) and Th2 (IL-4 and IL-10) cytokines, the tolerisation protocol down-regulated significantly only the IFN-gamma mRNA expression. More important, the recombinant alpha-gliadin induced a similar down-regulatory effect in mice immunised with a commercial preparation of wheat gliadin, that is a mixture of many different gliadin components. As the Th1 phenotype and the HLA-DQ8 molecule play a role in the pathogenesis of CD, our data underlined the potential usefulness of this recombinant protein for the immunomodulation of this disease.
Senger
Stefania
S
Istituto di Scienze dell' Alimentazione, CNR, via Roma 52, 83100 Avellino, Italy.
Luongo
Diomira
D
Maurano
Francesco
F
Mazzeo
Maria F
MF
Siciliano
Rosa A
RA
Gianfrani
Carmela
C
David
Chella
C
Troncone
Riccardo
R
Auricchio
Salvatore
S
Rossi
Mauro
M
D000281:Administration, Intranasal; D000818:Animals; D002446:Celiac Disease / Q000276:immunology; D002455:Cell Division; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D005903:Gliadin / Q000008:administration & dosage* / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D011503:Transglutaminases / Q000378:metabolism; D014908:Triticum / Q000276:immunology*
D016207:Cytokines; D011994:Recombinant Proteins; D005903:Gliadin; D011503:Transglutaminases