Background: The antigenic specificity of T cells occurs via generation and rearrangement of a functional T cell receptor (TCR). High throughput sequencing (HTS) platforms allow detailed assessment of TCR repertoire patterns in different diseases. There is limited data whether TCR repertoires are altered in IBD patients and whether common clones are shared between the blood and the gut. We hypothesized that pediatric UC patients possess unique TCR repertoires resulting from clonotypic expansions in the inflamed tissue.
Methods: Peripheral blood mononuclear cells (PBMCs) and rectal biopsies were collected from newly diagnosed pediatric UC patients and healthy controls. DNA was isolated and HTS was performed to determine the TCRβ repertoire. ImmunoSeq analysis software was used for analysis.
Results: Paired PBMCs and rectal biopsies were collected from 4 control subjects and 6 UC patients. In both patients and controls, the TCR repertoire was more clonal in the tissue, compared to the blood. Moreover, the repertoire was further restricted in both PBMCs and tissue of UC patients vs. controls, and in several patients, specific clones were highly expressed in the inflamed rectum (>5% of total clones). Despite a similar clinical phenotype, the frequency of shared common clones between patients was very low. However, several unique clones were upregluated only among UC patients and vice versa.
Conclusion: HTS of the TCR is a powerful tool for studying adaptive immune cell function in the gut. The oligoclonality observed among UC patients suggests specialization of unique mucosal T cell clones, that likely have a role in mediating tissue damage.
