CD8⁺ T Cell Immune Signatures Bridging Systemic Inflammation and Coronary Artery Injury in Kawasaki Disease

Abstract Kawasaki disease (KD) is an acute onset, childhood systemic vasculitis with the most important complication being coronary artery injury with aneurysm formation. In the pathogenesis of KD, innate immune overactivation is well recognized, but the role of adaptive immunity in the progression of vascular lesions is not completely understood. A local lesion in the coronary artery is thought to connect to the systemic inflammatory reaction through CD8 + T cells. In this review, we discuss evidence from peripheral blood immunophenotyping, single cell transcriptomics, TCR clonal repertoire profiling, human coronary artery pathology and KD like animal models to delineate CD8⁺ T-cell signatures and their proposed pathogenic mechanisms. The circulating CD8 + T cells from acute-phase patients have decreased numbers, increased activation markers, skewed subset distribution, and co-existent proliferative and CTL and exhaustion phenotype transcription profiles in conjunction with TCR clonal expansion. CD8 + T cells appear to infiltrate the coronary arterial lesions in human autopsy samples and CD8 + T cells induce coronary arteritis in murine models. Interestingly, classical perforin-granzyme-mediated cytotoxicity of lesional CD8 + T cells is not confirmed in human KD, underscoring a crucial gap between peripheral omics signatures, data in animal models and evidence in human tissues. The in situ effector mechanisms of disease driving CD8+ T cells subsets, and their feasibility as clinical biomarkers, warrant further investigation and may lead to precision risk stratification and targeted immunotherapies in KD related vascular complications, using multicenter prospective cohorts and paired blood and tissue functional assays.