This study showed dysregulated αβ T cell homeostasis with ongoing T cell activation and low-grade inflammation in 5-12-year-old CHD children who underwent early-life cardiac surgery with thymectomy, characterized by reduced naïve T cells and increased memory/effector and senescent-like T cells. There was also higher expression of inhibitory receptors on effector T cells and elevated suppressive gene expression in Tregs that may regulate immune overactivation.
ABSTRACT
Congenital heart disease (CHD) is a major global health problem. Although treatment and survival have impressively improved, many patients face comorbidities such as increased susceptibility to infection that may shorten their lives. As many children undergo cardiac surgery with concomitant thymectomy early in life, most studies of the immune system in patients with CHD have focused on the quantitative analysis of lymphocyte subpopulations, maturation, and T cell receptor repertoires, whereas knowledge of effector functions remains 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 to five to ten years after thymectomy, in comparison to age-matched healthy controls.
Children with CHD showed reduced T cell populations, a reduction of recent thymic emigrants (RTEs) and naive T cells, regulatory T cells with a higher suppressive phenotype, and, most importantly, high activation states of T cells, further reflected in higher granzyme and cytokine production. This reveals persistent alterations in T cell immunity years after early-life thymectomy in children with CHD, highlighting the need for long-term immune monitoring and providing a basis for understanding immune-related comorbidities in this patient population.