Testing safety of germinated rye sourdough in a celiac disease model based on the adoptive transfer of prolamin-primed memory T cells into lymphopenic mice.
The current treatment for celiac disease is strict gluten-free diet. Technical processing may render gluten-containing foods safe for consumption by celiac patients, but so far in vivo safety testing can only be performed on patients. We modified a celiac disease mouse model to test antigenicity and inflammatory effects of germinated rye sourdough, a food product characterized by extensive prolamin hydrolysis. Lymphopenic Rag1-/- or nude mice were injected with splenic CD4+CD62L-CD44high-memory T cells from gliadin- or secalin-immunized wild-type donor mice. We found that: 1) Rag1-/- recipients challenged with wheat or rye gluten lost more body weight and developed more severe histological duodenitis than mice on gluten-free diet. This correlated with increased secretion of IFNγ, IL-2, and IL-17 by secalin-restimulated splenocytes. 2) In vitro gluten testing using competitive R5 ELISA demonstrated extensive degradation of the gluten R5 epitope in germinated rye sourdough. 3) However, in nude recipients challenged with germinated rye sourdough (vs. native rye sourdough), serum anti-secalin IgG/CD4+ T helper 1-associated IgG2c titers were only reduced, but not eliminated. In addition, there were no reductions in body weight loss, histological duodenitis, or T cell cytokine secretion in Rag1-/- recipients challenged accordingly.


CONCLUSIONS
1) prolamin-primed CD4+CD62L-CD44high-memory T cells induce gluten-sensitive enteropathy in Rag1-/- mice. 2) Hydrolysis of secalins in germinated rye sourdough remains incomplete. Secalin peptides retain B and T cell stimulatory capacity and remain harmful to the intestinal mucosa in this celiac disease model. 3) Current antibody-based prolamin detection methods may fail to detect antigenic gluten fragments in processed cereal food products.
Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland;
Tobias L
TL
Freitag
Jussi
J
Loponen
Marcel
M
Messing
Victor
V
Zevallos
Leif C
LC
Andersson
Tuula
T
Sontag-Strohm
Päivi
P
Saavalainen
Detlef
D
Schuppan
Hannu
H
Salovaara
Seppo
S
Meri
D019264:Adoptive Transfer; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D002446:Celiac Disease / Q000276:immunology*; D055050:Diet, Gluten-Free; D004382:Duodenitis / Q000188:drug therapy / Q000276:immunology; D018525:Germination; D005983:Glutens / Q000276:immunology; D007422:Intestines / Q000382:microbiology; D008297:Male; D051379:Mice; D055315:Prolamins; D012434:Secale / Q000737:chemistry* / Q000254:growth & development / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000900:Anti-Bacterial Agents; D055315:Prolamins; D005983:Glutens
B cell; enteropathy; gluten; small intestine