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OBJECTIVE: We aimed to characterize CD4 T cell plasticity in human SLE by leveraging TCR repertoire features as markers of prior lineage states, integrating TCR and transcriptomic profiling to delineate plasticity patterns and evaluate their association with clinical disease activity.METHODS: We utilized T cell receptor (TCR) repertoire data as molecular signatures alongside a transcriptomic dataset. Using a large-scale ImmuNexUT database of autoimmune disease patients including 117 SLE cases, we quantified T cell plasticity across 13 fine-grained T cell-types. We analyzed 6,392 samples in total. We defined "cell-type" and "disease" signatures and evaluated plasticity by correlations between these signatures and by within-donor TCR clonotype overlap. Replication was performed in independent bulk and single-cell cohorts.RESULTS: We identified two orthogonal signatures of repertoire and transcriptome, the cell-type and disease signatures, allowing us to investigate CD4 T cell plasticity comprehensively. Among all possible patterns, the strongest signal was observed between effector regulatory T cells (eTreg) and Th1 cells, and this was replicated in an independent cohort. SLE Th1 cells exhibited Treg-like TCR features and transcriptomic profiles, and eTreg showed increased clonotype sharing with Th1 compared with healthy controls. Th1 "Tregness" score positively correlated with SLE disease activity.CONCLUSION: Our study identifies a Treg-associated Th1 state in human SLE, consistent with Treg-to-Th1 plasticity.