A mouse model for immunization with ex vivo virus-infected dendritic cells.
Dendritic cells (DCs) have been demonstrated to be an important if not essential inducer of cellular immune responses. The ability to grow these cells in vitro may open up new avenues for protective immunizations. In this study 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 but do not release infectious progeny virus. Ex vivo-infected DCs secrete interleukin-12 (IL-12) and induce a potent T helper (Th)1-like immune response when injected into mice. This was demonstrated by the generation of cytotoxic 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 primarily of the IgG2a isotype, consistent with the expansion of Th1 cells. Animals immunized with DCs infected with X-31 influenza virus and challenged with PR8 influenza virus cleared the infection faster than animals not vaccinated. Thus, infected DCs efficiently activate the cellular immune response and induce heterosubtypic immunity in mice.
López
C B
CB
Department of Microbiology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, New York, 10029, USA.
Fernandez-Sesma
A
A
Czelusniak
S M
SM
Schulman
J L
JL
Moran
T M
TM
D019264:Adoptive Transfer / Q000379:methods*; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology / Q000473:pathology / Q000821:virology; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology / Q000637:transplantation / Q000821:virology*; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D007156:Immunologic Memory; D009980:Influenza A virus / Q000145:classification / Q000276:immunology* / Q000472:pathogenicity; D007274:Injections, Intraperitoneal; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000473:pathology / Q000821:virology; D012008:Recurrence; D013045:Species Specificity; D013234:Stem Cells / Q000276:immunology / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000821:virology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D014771:Virion / Q000254:growth & development / Q000472:pathogenicity
D000956:Antigens, Viral