T-cell states in aortic dissection: from molecular immune profiling toward causal and translational validation

Single-cell RNA sequencing and T-cell receptor profiling reveal substantial T-cell heterogeneity in aortic dissection (AD), but whether these responses contribute to vascular injury or reflect post-onset immune activation remains uncertain. This review evaluates human and experimental evidence by disease stage, tissue compartment, functional validation, T-cell specificity, and intervention timing, distinguishing descriptive profiling from evidence supporting causal and translational inference.

Human studies identify Th1/Th17-associated, CD8⁺ cytotoxicity-associated, and regulatory T-cell alterations, with stage-related differences in T-cell composition and clonality. Most evidence is cross-sectional and obtained after clinical onset. Antigen specificity, direct aortic-wall cytotoxicity, impaired Treg suppression, and T-cell-mediated aortic-wall injury remain unproven. Single-cell and TCR profiling identify candidate T-cell states and clonotypes for spatial and functional validation, not causal proof. Among candidate pathways, the IL-6-STAT3-IL-17 axis currently has the strongest AD-specific preclinical rationale, but existing interventions are largely non-T-cell-restricted and initiated before or during disease induction. Stronger causal attribution requires convergent human evidence, post-lesion T-cell-restricted perturbation, disease-progression endpoints, and rescue or target-engagement studies. The subacute phase after anatomical and haemodynamic stabilisation may offer a window to study persistent injury-amplifying T-cell responses, whereas early acute and perioperative immunomodulation remains unsupported.

Current evidence supports altered T-cell states after AD onset but does not establish an initiating role. Near-term priorities should be prospective biomarker validation and post-lesion mechanistic studies rather than T-cell-directed immuno-modulation during the early acute and perioperative phases. Clinical translation should await reproducible associations linked to stage-specific causal mechanisms and acceptable safety.