Abstract:
Background: The present study aims to detect, quantify and
analyze circulating nutritional antigen-specific T-cells in patients
with celiac disease (CeD) as well as inflammatory bowel disease (IBD),
thus comparing the specific T-cell response following barrier disruption
and antigen translocation.
Methods: The antigen-reactive T-cell enrichment (ARTE) technique
was applied allowing for a phenotypical and functional flow cytometric
analysis of rare nutritional antigen-specific T-cells, including the
CeD-causing gliadin (gluten), in the peripheral blood.
Results: Our study indicates that by applying the ARTE technique,
differences of gluten-specific T-cells as well as the differential
cytokine expression between the patient groups can be detected, even
without the burdening gluten re-exposure of the patients. CeD patients,
independent from the presence or absence of gluten exposure in their
current diet, featured an increase of the frequency of gliadin-specific
T-cells, which were characterized by a pro-inflammatory phenotype.
However, only for active CeD and a consecutive small intestinal barrier
breach, an increase of distinct nutritional T-cells could be detected.
Accordingly, frequency as well as pro-inflammatory phenotype of
nutritional antigen-specific T cells were highest in Crohn’s disease
patients with small intestinal inflammation whereas no significant
increase was observed in ulcerative colitis.
Conclusion: In summary, the ARTE method allows not only for
detection but also for functional analysis of these rare cells even in
healthy subjects. Applying this method, we were able to demonstrate that
for non-CeD-related nutritional antigens, small intestinal barrier
breach is mandatory for a peripheral antigen-specific T-cell.