Impaired neonatal natural killer-cell activity to herpes simplex virus: Decreased inhibition of viral replication and altered response to lymphokines |
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Authors: | Paul J Leibson Mary Hunter-Laszlo George S Douvas Anthony R Hayward |
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Institution: | (1) Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, 1400 Jackson Street, 80206 Denver, Colorado;(2) Department of Pediatrics, University of Colorado Health Sciences Center, 80262 Denver, Colorado;(3) Department of Microbiology, University of Colorado Health Sciences Center, 80262 Denver, Colorado |
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Abstract: | Human adult natural killer (NK) cells were recently demonstrated to inhibit herpes simplex virus (HSV) replicationin vitro. In this study we compared the ability of newborn and adult NK cells to inhibit HSV replication. Cord blood mononuclear cells (MNCs) from healthy, term newborns and MNCs from adults were analyzed for their percentage of Leu-11+ cells and comparedin vitro for their NK-cell activity against HSV-infected fibroblasts and the tumor cell line K562. Cord blood MNCs, compared with adult MNCs, had significantly lower percentages of Leu-11+ cells (5 vs 11%;P<0.01), less anti-K562 NK activity (6 vs 54 lytic units/107 cells;P<0.001), and less anti-HSV NK activity (5 vs 52% HSV plaque inhibition;P<0.02). Comparing individual neonates and adults with equal percentages of Leu-11+ cells, neonatal MNCs still had less NK activity against either target. When Leu-11+ MNCs were isolated using the fluorescence-activated cell sorter, neonatal Leu-11+ MNCs still inhibited HSV replication less than adult Leu-11+ MNCs (P<0.01). MNCs from some neonates had significant anti-K562 NK activity but poor anti-HSV NK activity, suggesting either nonidentical NK-cell subpopulations or specific suppression. Whereas neonatal NK activity against K562 was always augmented by prior exposure to either interferon (IFN) or interleukin-2 (IL-2), the neonatal NK activity against HSV-infected cells was only augmented for half of the neonates tested. Endogenous production of alpha-IFN and gamma-IFN by MNCs exposed to HSV-infected fibroblasts was the same for cells from neonates or from HSV-seronegative adults. More gamma-IFN was produced by MNCs from HSV-seropositive adults than from neonates or HSV-seronegative adults. These results suggest that although newborns have phenotypically identifiable NK cells and the capacity for IFN production, the ability of the NK cells to inhibit HSV replication is impaired, and their level of response and augmentation by specific lymphokines is target specific. |
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Keywords: | Herpes simplex virus natural killer cell interleukin-2 alpha-interferon gamma-interferon newborn immunity |
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