Development of Natural Killer Cytotoxicity during Childhood: Marked Increases in Number of Natural Killer Cells with Adequate Cytotoxic Abilities during Infancy to Early Childhood

Abstract

The cytotoxicity of natural killer (NK) cells against K562 cells and their responsiveness to interferon-alpha and interleukin 2 (IL-2) were studied throughout childhood using 51Cr-release and single-cell assays. Although NK activity was extremely low in the neonatal period, it almost reached the adult level during 1 to 5 mo of age and remained at that level thereafter. At the single-cell level, the binding, lytic, and recycling abilities were also depressed in the neonatal period, but these abilities improved conspicuously after this period; in particular, the lysis and recycling were at higher levels during 6 mo to 4 y of age. The absolute numbers of circulating cytotoxic NK cells were high during infancy to early childhood: they were 54 +/- 24 (mean +/- SD/mm3) in neonates, 115 +/- 48 in 1- to 5-mo-old infants, 121 +/- 42 in 6- to 12-mo-old infants, 93 +/- 26 in 1- to 4-y-old children, and 42 +/- 16 in adults. Interferon-alpha and IL-2 could enhance NK activity throughout childhood. The IL-2 enhancement was prominent especially in the neonatal period; IL-2 yielded a 2.5-fold increase in the number of cytotoxic cells and improved the recycling to the adult level. At older ages, interferon-alpha and IL-2 yielded 1.4- and 1.9-fold increases in the number of cytotoxic cells, respectively, but did not enhance the recycling. The increased number of NK cells with adequate cytotoxic abilities during infancy to early childhood indicates the predominance of NK immunity during these periods. IL-2 is a cytokine that induces high levels of NK cytotoxicity even in neonates.