HIV-1-specific CTL responses primed in vitro by blood-derived dendritic cells and Th1-biasing cytokines

Vaccine strategies designed to elicit strong cell-mediated immune responses to HIV Ags are likely to lead to protective immunity against HIV infection . Dendritic cells (DC) are the most potent APCs capable of priming both MHC class I- and II-restricted, Ag-specific T cell responses, Utilizing a syst em in which cultured DC from HIV-seronegative donors were used as APC to pr esent HIV-1 Ags to autologous T cells in vitro, the strength and specificit y of primary HIV-specific CTL responses generated to exogenous HIV-1 Nef pr otein as well as intracellularly expressed nef transgene product mere inves tigated, DC expressing the nef gene were able to stimulate Nef-specific CTL , with T cells from several donors recognizing more than one epitope restri cted by a single HLA molecule. Primary Nef-specific CTL responses were also generated in vitro using DC pulsed with Nef protein. T cells primed with N eF-expressing DC (via protein or transgene) were able to lyse MHC class I-m atched target cells pulsed with defined Nef epitope peptides as well as new ly identified peptide epitopes, The addition of Th1-biasing cytokines IL-12 or IFN-alpha, during priming with Nef-expressing DC, enhanced the Nef-spec ific CTL responses generated using either Ag-loading approach. These result s suggest that this in vitro vaccine model may be useful in identifying imm unogenic epitopes as vaccine targets and in evaluating the effects of cytok ines and other adjuvants on Ag-specific T cell induction. Successful approa ches may provide information important to the development of prophylactic H IV vaccines and are envisioned to be readily translated into clinical DC-ba sed therapeutic vaccines for HIV-1.