naive T cell heterogeneity after neonatal thymectomy

The generation of new naive T-cells is dependent on thymic output, but in adults the naive T-cell pool is primarily maintained by peripheral proliferation. Naive T-cells have long been regarded as relatively quiescent cells but recently it was shown that IL-8 production is a signatory effector function of naïve T-cells, at least in newborns. With human aging naïve CD4 T-cell numbers decline but it is not clear whether this is accompanied by (functional) differentiation of naïve T-cells and loss of true naivety. Using a unique cohort of children and adolescents who underwent neonatal thymectomy, we demonstrate that the naive CD4 T-cell compartment in healthy humans is functionally heterogeneous and that this functional diversity is lost after neonatal thymectomy. Thymic regeneration later in life resulted in functional restoration of the naïve T-cell compartment. These data shed further light on functional differentiation within the naive T-cell compartment and the importance of the thymus in naive T-cell homeostasis.