Clinical and experimental gastroenterology · 2020
Circulating α4β7+ Memory T Cells in Pediatric IBD Patients Express a Polyclonal T Cell Receptor Repertoire.
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Gamliel Adir, Werner Lael, Pinsker Marina, Salamon Naomi, Weiss Batia, Shouval Dror S
Аннотация
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.
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.