Sustained αβ T Cell Effector Activity and Memory Expansion in Children with Congenital Heart Disease

Congenital heart disease (CHD) is a major global health problem. Although treatment has improved, children still face comorbidities that may shorten their life. Most studies of the immune system in people with CHD have focused on the quantitative analysis of lymphocyte subpopulations, maturation and T cell receptor repertoires, while knowledge of effector functions is limited. We analysed αβ T cell phenotypes, transcriptomes and functions in children with CHD who underwent cardiac surgery within a year of birth and were followed up five to ten years after thymectomy, in comparison to age-matched healthy controls. We show that children with CHD have immunological alterations, including reduced T cell populations, lower CD4+ or CD8+ T cell proportions, reduced proportions of recent thymic emigrants (RTEs) and naive cells, and an accumulation of memory T cell populations. Single-cell transcriptomics and functional assays revealed high activation states of T cells and higher granzyme and effector cytokine production in children with CHD. Our study provides a foundation for longitudinal studies in children, adults and the elderly to unravel the cause of increased morbidity and mortality in these patients.