Vaccinia virus-related events and phenotypic changes after infection of dendritic cells derived from human monocytes

The in vitro interactions between vaccinia Virus (VV) and monocyte-derived human dendritic cells (DC) have been studied to gain a better understanding of the mechanisms involved in the induction of an immune response by VV. T his work showed that VV binds to DC less efficiently than to HeLa cells (He La). Capping of viral antigens on the DC surface and electron microscopic e xaminations suggested that VV enters into DC mainly by endocytosis instead of fusion as for Hela. Early viral-encoded proteins were expressed in DC bu t late viral proteins and viral DNA synthesis did not occur. Nevertheless, when successfully infected, DC expressed a similar amount of a foreign, vir al-encoded protein, as HeLa, if the early component of the p7.5 promoter wa s used. VV infection did not lead to DC maturation as determined by followi ng the level of several cell surface markers associated with maturation, bu t an inhibition of the expression of the costimulatory molecule CD80 was no ticed. The proliferation of allogeneic peripheral blood lymphocytes (PBL) w as stimulated by VV-infected DC or inhibited depending on the particular do nor lymphocytes employed. PBL from W-vaccinated individuals with good memor y responses to VV antigens proliferated in the presence of infected autolog ous DC. PBL from individuals with poor memory responses to VV and one unvac cinated individual also proliferated, albeit to a lower level, in the prese nce of infected autologous DC. These results suggest that VV-infected DC co uld both stimulate memory cells and prime naive cells in vitro. (C) 2000 Ac ademic Press.