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Circulating ?4?7+ Memory T Cells in Pediatric IBD Patients Express a Polyclonal T Cell Receptor Repertoire

ABSTRACT: Background The integrin ?4?7 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 ?4?7+ and ?4?7? populations. DNA was extracted from each subset and subjected to next-generation sequencing of the TCR?. Different repertoire characteristics were compared between ?4?7+ and ?4?7? subsets for each subject, and between groups. Results The percentages of memory T cells and ?4?7+ cells were comparable between groups. ?4?7+ 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 ?4?7+ and ?4?7? 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 ?4?7+ memory T cells exhibited a polyclonal repertoire in both control subjects and patients with active inflammatory bowel disease, with high rates of overlap with ?4?7? 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.

SUBMITTER: Gamliel A

PROVIDER: S-EPMC7537844 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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