Functional analyses of cord blood natural killer cells and T cellsa distinctive interleukin-18 response

Objective: To search for the functional property of cord blood (CB) cells, the effects of interleukin-18 (IL-18) on interferon-γ (IFN-γ) production of T cells or natural killer (NK) cells were compared between CB and adult peripheral blood (PB). Materials and Methods: T cells, CD45RA⁺ T cells, and NK cells were purified from CB and adult PB mononuclear cells using magnetic beads or a cell sorter. After stimulation with or without IL-18 in the presence of IL-12 for 48 hours (NK cells) or 72 hours (T cells or CD45RA⁺ T cells), IFN-γ concentration was measured in each subset. Although IL-18 induced significant IFN-γ production from both CB and adult PB T cells in the presence of IL-12, the IFN-γ levels from CB T cells were lower than those from adult PB T cells. However, CD45RA⁺ T cells from CB and from adult PB produced similar levels of IFN-γ after stimulation with IL-18 + IL-12. On the other hand, CB NK cells exhibited higher IFN-γ production and CD69 expression than adult PB NK cells after stimulation with IL-18 + IL-12. Cytolytic activity of CB NK cells increased to a level comparable to that of adult PB NK cells after the same IL-18/IL-12 stimulation. Conclusions: These results suggest that a low response of CB T cells to IL-18 is due to a higher proportion of naive (CD45RA⁺) T cells in CB, which may be one of the factors responsible for the neonatal immaturity of the immune system as well as the low incidence of graft-vs-host disease in patients receiving CB stem cell transplantation. On the other hand, a high response of CB NK cells to IL-18 may contribute to the host defense during the neonatal period and antitumor effects in CB stem cell transplantation.