Activation of Human Natural Killer Cells by Herpes Simplex Virus Type 1-Infected Cells

Abstract

Human natural killer (NK) cells were shown to be much more cytolytic for WISH cells infected with herpes simplex virus type 1 (HSV-1) than for uninfected cells during 18-hour ⁵¹Cr release assays. Cold-target competition experiments involving high cold target to radiolabeled target cell ratios demonstrated that infected cells specifically competed for lytic activity against infected cell targets, and, therefore, the infected cells were not inherently more sensitive to lysis than uninfected cells. In contrast to these findings, depletion experiments involving low ratios of cold HSV-1-infected targets to labeled infected target cells resulted in increased lytic activity against uninfected cell targets. This finding suggested that NK effectors with specificity for WISH cell surface determinants had become highly activated during the depletion incubation. The addition of interferon alpha and particularly interleukin 2 to NK cytotoxicity assays enhanced NK cytolytic activity against both infected and uninfected target cells in a dose-dependent manner. Interleukin 1 did not give this effect. However, the enhanced lytic activity of NK cells following exposure to low doses of infected cell cold targets cannot be explained solely on the basis of release of the three lymphokines tested, since interleukin 1 was not effective, interleukin 2 was not detected in culture supernatants derived from the competition experiments, and NK cells preferentially lyse HSV-1-infected target cells independent of the enhancing effects of interferon. Together, the results indicated that NK cells recognize and bind to specific target cell surface structures which may, in turn, enhance their lytic activity.

The Immune Response to Ocular Herpes Simplex Virus Type 1 Infection

“…The NK cell mechanism of resistance should not be overlooked in any consideration of herpes viral infection. It has been amply demonstrated in patients and in experimental animals that NK cells and macrophages are key mediators of viral resistance (55)(56)(57)(58)(59)(60)(61)(62)(63). Thus, separate from, and without the direct intervention of antigen-specific T lymphocytes, NK cells and macrophages mediate an important component of resistance to herpes virus and resolution of the herpes viral infection of a tissue such as the cornea.…”

Role of histamine in natural killer cell-dependent protection against herpes simplex virus type 2 infection in mice

“…In spite of the numerous studies showing that NK cells specifically recognize HSV-infected target cells in vitro (3,7,9,10,18,21,24,27,28), evidence that NK cells play a major role in defense against HSV-1 and HSV-2 in vivo is scarce. Bukowski and Welsh (5) reported that NK cells failed to protect mice from lethal HSV-1 infection, on the basis of the a Animals were treated with the respective compounds 24 h before inoculation of HSV-2 (7,500 PFU/ml).…”

“…Infection of target cells with viruses of the family Herpesviridae has been used to study interactions of NK cells with virusinfected cells in vitro. Herpes simplex virus type 1 (HSV-1) and HSV-2 infection enhances the susceptibility of target cells to NK cell-mediated cytotoxicity (3,7,10,18,24,27,28), and NK cells can inhibit the progression of HSV in infected targets (9,21). With this background information, we chose to study the role of NK cells in mice acutely infected with HSV-2, with special emphasis on the importance of histaminergic mechanisms.…”

Anti-Interferon Antibody Inhibits Natural Killer Cell Activity in HSV-2 Genital Infection in C57BL/6J Mice

“…Several studies have shown that human [19][20][21][22] and mouse [23] NK cell populations are heterogenous. In addition, several au thors [5,[19][20][21][22][23] have shown that NK cell activity against uninfected cells and HSV-infected cells may be regulated by different subsets of NK cells.…”