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

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.

Biological Analyses-Derived Translational Findings in the T Cell Receptor Alpha Chain Knockout Mouse as an Experimental Model for Ulcerative Colitis

“…Therefore, Zeissig et al and Gamliel et al examined the effect of vedolizumab on the phenotype of mucosal intrinsic layer T cells. Vedolizumab has been found not to affect the repertoire of T cells in LP or leukocyte trafficking in vivo [29,30]. However, administration of vedolizumab has been shown to alter macrophage populations, thereby markedly altering the expression of molecules related to microbial sensing, chemoattraction, and modulation of innate effector responses [29].…”