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

Abstract

The in vitro interactions between vaccinia virus (VV) and monocyte- derived human dendritic cells (DO) have been studied to gain a better understanding of the mechanisms involved in the induction of an immune response by W. This work showed that W binds to DO less efficiently than to HeLa cells (HeLa). Capping of viral antigens on the DO surface and electron microscopic examinations suggested that W enters into DO mainly by endocytosis instead of fusion as for HeLa. Early viral-encoded proteins were expressed in DO but late viral proteins and viral DNA synthesis did not occur. Nevertheless, when successfully infected, DC expressed a similar amount of a foreign, viral-encoded protein, as HeLa, if the early component of the p7.5 promoter was used. W infection did not lead to DO maturation as determined by following the level of several cell surface markers associated with maturation, but an inhibition of the expression of the costimulatory molecule CD80 was noticed. The proliferation of allogeneic peripheral blood lymphocytes (PBL) was stimulated by W-infected DC or inhibited depending on the particular donor lymphocytes employed. PBL from W-vaccinated individuals with good memory responses to W antigens proliferated in the presence of infected autologous DO. PBL from individuals with poor memory responses to W and one unvaccinated individual also proliferated, albeit to a lower level, in the presence of infected autologous DC. These results suggest that W- infected DO could both stimulate memory cells and prime naive cells in vitro. (C) 2000 Academic Press.