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

Persistent expansion of alloreactive T cell clones and phenotypic plasticity drive severe graft-versus-host disease in human transplant recipients.

• Why it matters: Understanding how T cell clones cause tissue injury is crucial for improving transplant outcomes and developing targeted therapies for graft-versus-host disease.
• What they did: Researchers integrated longitudinal TCR profiling, single-cell RNA sequencing, and spatial transcriptomics in 31 patients, developing DecompTCR to analyze clone dynamics and tissue niches.
• The result: Findings show that alloreactive clones persist and diversify, acquiring tissue-resident memory programs, with spatial hubs near crypt bases, linking T cell remodeling to epithelial injury and suggesting new biomarkers.