Human dendritic cells are phenotypically matured by Modified vaccinia virus Ankara and activate allogeneic CD4+ and CD8+ T cells

PASCUTTI MF; RODRÍGUEZ AM; MONACO D; DREXLER I; GHERARDI MM

Keystone, Colorado, USA

Simposio; Prevention of HIV/AIDS; 2009

Keystone Symposia

Modified vaccinia virus Ankara (MVA) is an attenuated vaccinia virus (VV) strain known to be an effective vaccine vector. It has been shown that MVA, unlike replicating VV strains, induces moderate phenotypic activation of monocyte-derived human dendritic cells (DCs) and the secretion of small amounts of pro-inflammatory cytokines. However, the functional profile of MVA-activated DCs has not been tested so far. In the context of vaccine development, it is important to understand how MVA activates DCs to induce an effective cellular immune response. Here, we infected DCs with an MVA-GFP strain and examined their phenotypic activation as well as their ability to produce IL-12 and to activate CD4+ and CD8+ T cells in a mixed lymphocyte reaction. We found that, at a MOI of 1, MVA induced a significant increase in CD86 and HLA-DR expression. Although HLA-DR increased both in infected (GFP+) and bystander (GFP-) DCs, CD86 only increased in bystander cells. In agreement with this, phenotypic activation was also observed when DCs were co-cultured with supernatant from infected DCs or with infected apoptotic DCs. Although MVA-infected mature DCs produced very low amounts of IL-12, they were able to induce an increase in the expression of the activation markers CD69 and CD38 on allogeneic CD4+ and CD8+ T cells. Taken together these studies indicate that MVA infection results in mature DCs that are able to activate allogeneic T cells in an IL-12 independent manner. Since MVA-infected DCs did not up-regulate co-stimulatory molecules, bystander non-infected DCs are probably implicated in this activation.