TGF-β is responsible for NK cell immaturity during ontogeny and increased susceptibility to infection during mouse infancy

Abstract

New-born and young mice are more susceptible to viral infections. Laouar and colleagues show this sensitivity is due in part to age-dependent TGF-β–mediated suppression of natural killer cell production. A large gap in our understanding of infant immunity is why natural killer (NK) cell responses are deficient, which makes infants more prone to viral infection. Here we demonstrate that transforming growth factor-β (TGF-β) was responsible for NK cell immaturity during infancy. We found more fully mature NK cells in CD11cdnR mice, whose NK cells lack TGF-β receptor (TGF-βR) signaling. Ontogenic maturation of NK cells progressed faster in the absence of TGF-β signaling, which results in the formation of a mature NK cell pool early in life. As a consequence, infant CD11cdnR mice efficiently controlled viral infections. These data thus demonstrate an unprecedented role for TGF-β in ontogeny that can explain why NK cell responses are deficient early in life.