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
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
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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