Spatiotemporal single-cell profiling reveals T cell clonal dynamics and phenotypic plasticity in human graft-versus-host disease.

Severe graft-versus-host disease is linked to persistent expansion of alloreactive T cell clones that acquire tissue-resident memory programs during migration to epithelium.

• Why it matters: Understanding how human T cell clones drive epithelial injury in graft-versus-host disease is limited, hindering targeted interventions and biomarker development for early detection and treatment.
• What they did: The study analyzed 31 transplant recipients using longitudinal TCR profiling, single-cell RNA sequencing, and spatial transcriptomics, developing DecompTCR to track T cell clonal dynamics and phenotypes.
• The result: Persistent alloreactive clone expansion and spatial hubs of CD8+ T RM cells near crypt bases correlate with epithelial injury, suggesting early-repertoire dynamics and spatial burden as potential biomarkers.