These findings suggest that the extent of active T cell recognition of environmental allergens has been hitherto underestimated, and further that these responses may frequently be initiated in very early life. Additionally, these findings reinforce the notion that qualitative (as opposed to quantitative) variations in specific T cell reactivity ultimately determine allergen responder phenotype.

Detailed analysis of cytokine responses in this very young age group have the potential to uncover subtle relationships between in vivo and in vitro allergen reactivity which may be less clear in adults, in whom T-cell response patterns are modified via chronic stimulation. The present findings which suggest potentially important roles for IL-9 and IL-10 in the early phase of allergic disease, may be one such example.

ABSTRACT. The cytotoxicity of natural killer (NK) cells virus exposure of neonates can result in severe infection, which against K562 cells and their responsiveness to interferon-is explained by the depressed activity of NK cells (5)(6)(7)(8). Although a and interleukin 2 (IL-2) were studied throughout child-viral infections cause various clinical pictures at different levels hood using S'Cr-release and single-cell assays. Although of ontology (9), very little is known about the developmental NK activity was extremely low in the neonatal period, it profile of NK cytotoxicity during childhood. almost reached the adult level during 1 to 5 mo of age andIt is known that the number of lymphocytes in the peripheral remained at that level thereafter. At the single-cell level, blood varies widely among different ages of childhood. Neverthe binding, lytic, and recycling abilities were also de-theless, NK activity usually represents the cytotoxicity of a given pressed in the neonatal period, but these abilities improved number of lymphocytes (2). Although morphologic examination conspicuously after this period; in particular, the lysis and and surface marker analysis have been commonly used to deterrecycling were at higher levels during 6 mo to 4 y of age. mine the number of NK cells (2, lo), there have been conflicting The absolute numbers of circulating cytotoxic NK cells reports regarding the relationship between the NK cell number were high during infancy to early childhood: they were 54 and NK activity; the percentages of large granular lymphocytes f 24 (mean f SD/mm3) in neonates, 115 f 48 in 1-to 5-and CD16' cells in neonates are similar to those in adults (1 1, mo-old infants, 121 + 42 in 6-to 12-mo-old infants, 93 + 12), but NK activity is depressed in neonates (6, 13, 14). A single-26 in 1-to 4-y-old children, and 42 f 16 in adults. Inter-cell cytotoxicity assay allows the determination of the number feron-a and IL-2 could enhance NK activity throughout of NK cells with cytotoxic abilities (2, 15). childhood. The IL-2 enhancement was prominent espe-The purpose of our study was to investigate the developmental cially in the neonatal period; IL-2 yielded a 2.5-fold in-profile of the cytotoxicity mediated by circulating NK cells crease in the number of cytotoxic cells and improved the during childhood using 51Cr-release and single-cell assays. In our recycling to the adult level. At older ages, interferon-a and study, we demonstrate the normalization of NK cell functions IL-2 yielded 1.4-and 1.9-fold increases in the number of after the neonatal period and an increased number of the cells cytotoxic cells, respectively, but did not enhance the recy-during infancy to early childhood. cling. The increased number of NK cells with adequate cytotoxic abilities during infancy to early childhood indi- MATERIALS AND METHODScates the predominance of NK immunity during these periods. IL-2 is a cytokine that induces high levels of NK Subjects. Cord blood samples were collected immediately after cytotoxicity even in neonates. (...

SUMMARYWe classified CD56+ CD3− natural killer (NK ) cells into CD2− CD56dim (CD2− NK), CD2+ CD56dim (CD2+ NK) and CD2+ CD56bright populations, and investigated mainly functional differences between the former two populations. CD2− and CD2+ NK cells were the same in their morphology and several surface molecules except for CD2. The percentages of CD2− NK cells in total NK cells were higher in the cord blood and bone marrow than in the peripheral blood of adults or children. Freshly isolated CD2− NK cells had CD2 in the cytoplasm, and gradually expressed it on the surface upon incubation with interleukin-2 ( IL-2). These results demonstrated that CD2 is an antigen which appears on the surface during the maturation of NK cells. The granule-mediated cytotoxicities, which are mainly performed by the perforin molecule, of CD2+ NK cells against K562 and Daudi cells were higher than those of CD2− NK cells, and they were inhibited to the levels of CD2− NK cells by the addition of a blocking anti-CD2 monoclonal antibody (mAb). Fas ligand ( FasL) mRNA was expressed in freshly isolated CD2+ NK cells but not in the CD2− NK cells. Neither freshly isolated NK populations showed FasLmediated cytotoxicity, and only CD2+ NK cells lysed Fas-transfected targets after the 24-hr incubation with IL-2. Based on these results, CD2− NK cells have already developed granulemediated cytotoxicity equal to that of CD2+ NK cells except for the CD2-associated activity, but they, unlike CD2+ NK cells, totally lack FasL-mediated cytotoxicity. These findings suggest that FasL-mediated cytotoxicity may be acquired at more mature stages of NK-cell maturation than granule-mediated cytotoxicity.