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

Adir Gamliel; Lael Werner; Marina Pinsker; Naomi Salamon; Batia Weiss; Dror S Shouval

doi:10.2147/CEG.S271565

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

Clin Exp Gastroenterol. 2020 Oct 2:13:439-447. doi: 10.2147/CEG.S271565. eCollection 2020.

Authors

Adir Gamliel^{1

2}, Lael Werner^{1

2}, Marina Pinsker^{1

3}, Naomi Salamon¹, Batia Weiss^{1

2}, Dror S Shouval^{1

2}

Affiliations

¹ Pediatric Gastroenterology Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel.
² Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
³ Institute of Nanotechnology and Advanced Materials, Bar Ilan University, Ramat Gan, Israel.

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; T cells; TCR; immune repertoire; integrin; α4β7.