Induction of potent human immunodeficiency virus type 1-specific T-cell-restricted immunity by genetically modified dendritic cells

A novel technology combining replication- and integration-defective human i mmunodeficiency virus type I (HIV-1) vectors with genetically modified dend ritic cells was developed in order to induce T-cell immunity. We introduced the vector into dendritic cells as a plasmid DNA using polyethylenimine as the gene delivery system, thereby circumventing the problem of obtaining v iral vector expression in the absence of integration. Genetically modified dendritic cells (GMDC) presented viral epitopes efficiently, secreted inter leukin 12, and primed both CD4(+) and CD8(+) HIV-specific T cells capable o f producing gamma interferon and exerting potent HIV-1-specific cytotoxicit y in vitro. In nonhuman primates, subcutaneously injected GMDC migrated int o the draining lymph node at an unprecedentedly high rate and expressed the plasmid DNA. The animals presented a vigorous HIV-specific effector cytoto xic-T-lymphocyte (CTL) response as early as 3 weeks after a single immuniza tion, which later developed into a memory CTL response. Interestingly, anti bodies did not accompany these CTL responses, indicating that GMDC can indu ce a pure Th1 type of immune response. Successful induction of a broad and long-lasting HIV-specific cellular immunity is expected to control virus re plication in infected individuals.