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

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.