Early-life thymectomy enhances persistence of fetal-derived γδ T cells in children with congenital heart disease

Abstract Congenital heart disease (CHD) is the most common birth defect in newborns, often requiring surgical correction with thymectomy that is known to affect the T-cell pool and subsequent disease susceptibility. Studies of γδ T cells, which develop as ontogenetic waves, are rare in this context. Here, γδ T cells and αβ T cells were investigated in children with CHD, who underwent cardiac surgery shortly after birth. A reduced thymic activity and perturbations in postnatal-derived T cells were evident at 5–12 years post-surgery. Fetal-derived CD161hiNKG2A+ Vγ9Vδ2 T cells, which retained their functionality, showed elevated abundance. An increase of TRDJ3+ γδ T cell clones in pediatric CHD patients, but not in a confirmatory group of neonates prior to cardiac surgery, was identified. This study provides insight into the postnatal adaptation of γδ T cells in relation to thymic output and identifies persistence of fetal-derived Vγ9Vδ2 T cells in pediatric CHD patients.