T Cell Repertoire Homogeneity and Blood-Gut Overlap in Patients With Inflammatory Bowel Disease

BACKGROUND & AIMS: Inflammatory bowel disease (IBD) causes a marked increase in the number of T cells in the in-testinal mucosa. Debate exists about whether these excess cells arise from local clonal proliferation or recruitment from the periphery. METHODS: CD8+ T cells were sorted from colon biopsy specimens and blood for T-cell receptor (TCR) beta-chain sequencing. Biopsy specimens from inflamed or uninflamed colon from ulcerative colitis or Crohn's disease cohorts were compared with colon biopsy specimens from people without IBD, as well as with autologous blood alpha 4 beta 7+, alpha 4 beta 7-effector/memory, terminal effector/memory CD45RA(+) T cell, and mucosal-associated invariant T-cell CD8 subpopulations. RESULTS: CD8 TCR diversity in mucosa and blood did not correlate with inflammation. Repertoire overlap between any distinct locations of a given person's colon was consistently high, although often lower between inflamed and uninflamed sites. CD8 TCR repertoires overlapped between the colon and each peripheral blood subpopulation studied, with the highest overlap seen for integrin alpha 4 beta 7+ T cells. Inflamed tissue consistently overlapped more than uninflamed tissue with each blood subpopulation. CONCLUSIONS: CD8 T-cell clones are spread homogenously throughout the length of the colon. Although TCR repertoire overlap is greater within than between inflamed and uninflamed colon segments, a similar TCR diversity in both argues against local clonal expansion being the main source of excess cytotoxic T cells in inflamed mucosa. Rather, the increased TCR overlap observed between blood and inflamed mucosa supports the significance of T-cell trafficking in IBD pathogenesis, particularly concerning alpha 4 beta 7+ T-cell populations.