Human Monocyte-Mediated Cytotoxicity Against Herpes Simplex Virus-Infected Cells: Activation of Cytotoxic Monocytes by Free and Liposome-Encapsulated Lymphokines

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Abstract
Human peripheral blood monocytes were incubated with free or liposome- encapsulated human lymphokines containing macrophage-activating factor (MAF) and tested for their effect on herpes simplex virus (HSV)-infected target cells. Activated monocytes lysed allogeneic HSV type 2 (HSV-2)-infected whole human embryo cells and xenogeneic BALB/c mouse embryo cells (10E2) without any significant effect on uninfected cells, as measured by release of 51Cr from target cells after 18 h of cocultivation. Kinetic studies revealed that lysis of virus-infected cells occurred by 10 h following cocultivation with activated monocytes. The inability of free MAF or supernatants from MAF-acti- vated monocytes to lyse HSV-2-infected cells suggested that direct monocyte- target cell contact is required for monocyte-mediated cytotoxicity of the virus- infected cells. Monocytes activated with MAF suppressed the production of HSV-2 and HSV-1 from virus-infected cells more than control monocytes did. In addition, monocytes treated with liposome-encapsulated MAF selectively destroyed HSV-2-infected cells but left uninfected cells unharmed. The capacity of liposome-encapsulated immunomodulators to activate human monocytes to selectively lyse HSV-2-infected cells has potential therapeutic benefit and should be evaluated in vivo.