Decreased T cell stimulatory capacity of monocyte-derived human macrophages following herpes simplex virus type 1 infection

Macrophages play a central role in establishing a specific immune response by acting as professional antigen presenting cells (APC) for T cells leadin g to a vigorous immune response. In order to analyze if Herpes simplex Viru s (HSV) type 1 infection might affect the macrophage APC-function, monocyte -derived human macrophages were infected with HSV-1 strain F in vitro. Cocu ltures with allogeneic T cells revealed a strongly impaired stimulatory cap acity of HSV-infected macrophages compared to uninfected controls which was not owing to a productive viral infection in macrophages. An increased exp ression of Fas ligand (FasL/CD95L) was detected in MSV-infected macrophages by FAGS analysis. Although the majority of the macrophages expressed high levels of Fas (CD95/Aps-1), the HSV-induced upregulation of FasL did not re sult in an increased autocrine apoptosis of macrophages which might be rela ted to endogenous expression of the apoptosis inhibitor FLICE inhibitory pr otein (FLIP). However, substantial apoptosis occurred in peripheral T cells as well as Fas-sensitive Jurkat T cells when cocultured with MSV-infected macrophages. These findings suggest that the paracrine killing of activated T cells by FasL expressing APC might be a novel strategy of immune evasion by HSV.