Intravenous or intranasal administration of gliadin is able to down-regulate the specific immune response in mice.
The mucosal lesion in coeliac disease (CD) represents an immunologically mediated injury triggered by gliadin and is restricted by a particular assortment of major histocompatibility complex (MHC) class II genes. Therefore, immunomodulatory strategies to tolerize gliadin-specific, class II-restricted T-cell responses could represent an alternative to current treatments of CD, which are based on a gluten-free diet. In this study, BALB/c mice derived from a gluten-free diet colony were tolerized by either intranasal (i.n.) or intravenous (i.v.) administration of single or multiple doses of gliadin. While a single dose failed to induce tolerance, a significant decrease in gliadin-specific T-cell proliferation was detected (P < 0.001) after multiple i.n. or i.v. administrations. No significant difference in antibody titre was detected for antigen-specific immunoglobulin G (IgG) or the IgG1 subclass, but a lower IgG2a-specific titre was observed. Both interferon-gamma (IFN-gamma) and interleukin (IL)-2 expression, measured by enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR), were reduced on antigen administration, both i.v. and i.n. Neither regimen showed a regulatory effect on IL-4 production. As T helper 1 (Th1) cytokines seem to be important in the pathogenesis of CD, our data therefore highlight the potential of i.n. and i.v. routes for the design of useful immunomodulatory strategies for CD.
Rossi
M
M
Institute of Food Science and Technology, CNR, Avellino, Italy.
Maurano
F
F
Caputo
N
N
Auricchio
S
S
Sette
A
A
Capparelli
R
R
Troncone
R
R
D000281:Administration, Intranasal; D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D015536:Down-Regulation; D005260:Female; D005903:Gliadin / Q000008:administration & dosage / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D007275:Injections, Intravenous; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
D007074:Immunoglobulin G; D007376:Interleukin-2; D015847:Interleukin-4; D007371:Interferon-gamma; D005903:Gliadin