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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)439-447
Number of pages9
JournalClinical and Experimental Gastroenterology
Volume13
DOIs
StatePublished - 2020

Keywords

  • IBD
  • Immune repertoire
  • Integrin
  • T cells
  • TCR
  • α4β7

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