A mouse model for immunization with ex vivo virus-infected dendritic cells

Dendritic cells (DCs) have been demonstrated to be an important if not esse ntial inducer of cellular immune responses. The ability to grow these cells in vitro may open up new avenues for protective immunizations. In this stu dy we have analyzed the virus-specific memory response generated following immunization with Ex vivo-infected bone marrow-derived dendritic cells. We demonstrate that mouse DCs are efficiently infected with influenza virus bu t do not release infectious progeny virus. Ex vivo-infected DCs secrete int erleukin-1a (IL-12) and induce a potent T helper (Th)1-like immune response when injected into mice. This was demonstrated by the generation of cytoto xic T lymphocytes, the production of high levels of gamma -interferon, and undetectable levels of IL-4 upon in vitro restimulation of splenocytes from immunized animals. In addition, the virus-specific antibody response is pr imarily of the IgG2a isotype, consistent with the expansion of Th1 cells, A nimals immunized with DCs infected with X-31 influenza virus and challenged with PR8 influenza virus cleared the infection faster than animals not vac cinated. Thus, infected DCs efficiently activate the cellular immune respon se and induce heterosubtypic immunity in nice, (C) 2000 Academic Press.