DENDRITIC CELLS EFFICIENTLY INDUCE PROTECTIVE ANTIVIRAL IMMUNITY

Cytotoxic T lymphocytes (CTL) are essential for effective immunity to various viral infections. Because of the high speed of viral replicati on, control of viral infections imposes demanding functional and quali tative requirements on protective T-cell responses. Dendritic cells (D C) have been shown to efficiently acquire, transport, and present anti gens to naive CTL in vitro and in vivo. In this study, we assessed the potential of DC, either pulsed with the lymphocytic choriomeningitis virus (LCMV)-specific peptide GP33-41 or constitutively expressing the respective epitope, to induce LCMV-specific antiviral immunity in viv o. Comparing different application routes, we found that only 100 to 1 ,000 DC had to reach the spleen to achieve protective levels of CTL ac tivation. The DC-induced antiviral immune response developed rapidly a nd was long lasting. Already at day 2 after a single intravenous immun ization with high doses of DC (1 x 10(5) to 5 x 10(5)), mice were full y protected against LCMV challenge infection, and direct ex vivo cytot oxicity was detectable at day 4 after DC immunization. At day 60, mice were still protected against LCMV challenge infection. Importantly, p riming with DC also conferred protection against infections in which t he homing of CTL into peripheral organs is essential: DC immunized mic e rapidly cleared an infection with recombinant vaccinia virus-LCMV fr om the ovaries and eliminated LCMV from the brain, thereby avoiding le thal choriomeningitis. A comparison of DC constitutively expressing th e GP33-41 epitope with exogenously peptide-pulsed DC showed that in vi vo CTL priming with peptide-loaded DC is not limited by turnover of pe ptide-major histocompatibility complex class I complexes. We conclude that the priming of antiviral CTL responses with DC is highly efficien t, rapid, and long lasting. Therefore, the use of DC should be conside red as an efficient means of immunization for antiviral vaccination st rategies.