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

Authors Gamliel A, Werner L, Pinsker M, Salamon N, Weiss B, Shouval DS

Received 10 July 2020

Accepted for publication 21 August 2020

Published 2 October 2020 Volume 2020:13 Pages 439—447

DOI https://doi.org/10.2147/CEG.S271565

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Wing-Kin Syn


Adir Gamliel,1,2 Lael Werner,1,2 Marina Pinsker,1,3 Naomi Salamon,1 Batia Weiss,1,2 Dror S Shouval1,2

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

Correspondence: Dror S Shouval
Pediatric Gastroenterology Unit, Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Ramat Gan, Israel
Tel +972-3-5305006
Email dror.shouval@gmail.com

Background: The integrin α 4β 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 α 4β 7+ and α 4β 7 populations. DNA was extracted from each subset and subjected to next-generation sequencing of the TCRβ. Different repertoire characteristics were compared between α 4β 7+ and α 4β 7 subsets for each subject, and between groups.
Results: The percentages of memory T cells and α 4β 7+ cells were comparable between groups. α 4β 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 α 4β 7+ and α 4β 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: α 4β 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 α 4β 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.

Keywords: IBD, TCR, integrin, α 4β 7, T cells, immune repertoire

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