Single-cell sequencing reveals T cell clonal patterns in healthy donors and ulcerative colitis patients.

This observational study utilized single-cell T cell receptor and RNA sequencing to characterize T cell repertoires in 333,088 cells derived from healthy donors and patients with ulcerative colitis (UC). The analysis focused on clonal group distribution, phenotypic diversity, and dispersion patterns within the colon and peripheral blood. No intervention was administered, and the study design is cross-sectional in nature.

In healthy donors, blood-colon clonal sharing was limited. Clonal sharing by T cell population was highest in cytotoxic T effector memory (Tem) populations and lowest in regulatory T cells (Tregs). Within the healthy colon, high clonal sharing occurred independent of anatomic distance and was associated with high intra-clonal phenotypic diversity. Regarding dispersion, cytotoxic and Th17 populations showed high dispersion, whereas Tregs were compartmentalized. Clonal lineages dispersed across blood and colon sites with upregulated trafficking markers, suggesting active movement between tissues. Conversely, lineages dispersed across colon sites showed upregulated residency markers, suggesting intra-colon repertoire sharing is mediated by long-term, slow-moving clonal groups.

In UC patients, Treg distribution expanded across inflamed sites. CD8 Tem clonal groups demonstrated increased dispersion regardless of the presence of inflammation. The study did not report adverse events, serious adverse events, discontinuations, or specific tolerability data. Key limitations include the observational nature of the data, which precludes causal inference regarding disease mechanisms. The findings describe immune repertoire characteristics but do not inform clinical management or therapeutic decisions for ulcerative colitis.