Human natural killer cells fail to kill herpes simplex virus type 1-infected term villus trophoblast cells

Abstract

Summary The study was undertaken to determine if HSV infection of trophoblast cells would alter the general resistant state of trophoblast cells to MHC non-restricted cell-mediated cytotoxicity. The NK cell activity against HSV-infected human term placental trophoblast cells was investigated. In a 12-hour 51 Cr release assay, PBMC, or immunosorted peripheral blood CD56 + NK cells from healthy donors were found not to lyse HSV-1-infected trophoblast cells, while HSV-1-infected placental fibroblast cells were preferentially lysed when using the same experimental set-up. Furthermore, using cold target competition assay, no inhibition of NK cell activity against the susceptible target cell K562 was noted when using HSV-infected or uninfected trophoblast cells. Inversely, both HSV-infected and uninfected fibroblast cells demonstrated a competitive inhibition of NK cell lysis of K562 cells. The observed differences between the susceptibility of HSV-infected placental trophoblast and fibroblast cells to NK lysis could not be explained by a difference in the surface expression of HSV-antigens or transferrin receptors. Additionally, no significant differences were observed for de novo production of IFN by effector cells during the cocultivation with HSV-infected trophoblast and fibroblast cells that would explain the observed discrepancies in NK susceptibility. Consequently, these in vitro results suggest that the observed resistance of trophoblast cells to maternal cell-mediated lysis is not modified by HSV-1 infection and that the peripheral blood NK cells are not involved in the prevention of a possible vertical HSV spread through infected trophoblast cells.