Circulating α4β7⁺ Memory T Cells in Pediatric IBD Patients Express a Polyclonal T Cell Receptor Repertoire

Abstract

Background

The integrin α4β7 is highly expressed on activated T cells and is thought to direct homing of lymphocytes to the intestine. Since ulcerative colitis (UC) and Crohn’s disease (CD) are characterized by mucosal oligoclonal T cells’ expansion, we aimed to assess whether similar repertoire features are identified in circulating gut-specific memory T cells.

Methods

Memory CD3⁺ T cells were isolated from blood samples of control subjects and patients with active UC or CD and then FACS-sorted into α4β7⁺ and α4β7⁻ populations. DNA was extracted from each subset and subjected to next-generation sequencing of the TCRβ. Different repertoire characteristics were compared between α4β7⁺ and α4β7⁻ subsets for each subject, and between groups.

Results

The percentages of memory T cells and α4β7⁺ cells were comparable between groups. α4β7⁺ memory T cells displayed a polyclonal distribution, in control subjects and in UC or CD patients, with similar indices of diversity. Strikingly, the clonal overlap between α4β7⁺ and α4β7⁻ T cells for each subject in all three groups was high, ranging between 20%–50%. We were unable to identify shared T cell clones that were specific to one of the groups.

Conclusion

α4β7⁺ memory T cells exhibited a polyclonal repertoire in both control subjects and patients with active inflammatory bowel disease, with high rates of overlap with α4β7⁻ memory T cells. Our study, along with additional recent reports, may suggest that the suppression of intestinal inflammation by vedolizumab is independent of the drug’s effect on T cell migration to the gut.

Keywords:

• IBD
• TCR
• integrin
• α4β7
• T cells
• immune repertoire

Disclosure

This study was funded by a research grant from Takeda. Dr Dror Shouval reports grants from Takeda, during the conduct of the study. The authors report no other potential conflicts of interest for this work.