FETAL NATURAL-KILLER-CELL FUNCTION IS SUPPRESSED

Previous studies have reported reduced natural killer (NK) cell activi ty in cord blood (CB) compared with adult blood mononuclear cell popul ations. Using a non-radioactive killing assay, we have verified these findings suggesting that either the fetal NK cell function is suppress ed or that these cells are functionally immature. We have shown that C B NK cells are functional, since activating them with cytokines known to activate adult NK cells [interleukin-2 (IL-2), IL-12 and IL-15] inc reased activation. However, resting the cells, which enhanced adult NK cell activity (P<0.01), had no effect on fetal NK cells (P=0.2). Thes e results suggested that fetal NK cells have the capacity to kill, but this is suppressed in vitro. This hypothesis was strengthened by our observation that eight of nine CB mononuclear cell populations had the ir NK activity restored by freeze-thawing, whereas four of five adult peripheral blood mononuclear cells had a reduced killing ability on fr eeze-thawing. Freeze-thawing removes a population of cells that suppre sses CB NK cell function. To determine which was the case we performed extensive phenotypic analysis of the CB populations pre-and post-free zing and found that the percentage of the CD3(-) CD56(+) population wi thin CB increased significantly (P<0.0005 by paired t-test) with freez ing, whereas freeze-thawing had no effect on this population within a normal adult peripheral blood mononuclear cell population. Our data su ggest that within CB there is a population of cells, as yet undefined, which may be inhibiting NK cell function. This report therefore shows clear differences between NK cells within the adult periphery and in CB, and may lead to a better understanding of events occurring in vivo .