Induction of tumor peptide-specific cytotoxic T cells under serum-free conditions by mature human dendritic cells

Tumor vaccination strategies using antigen-pulsed dendritic cells (DC) are currently under development. We established an in vitro system using cultur ed DC from HLA-typed volunteers for the induction of tumor peptide-specific CD8(+) T cells. The strength and specificity of the resulting CTL response s were investigated. For stimulation of syngeneic CD8(+) T cells two well-d efined DC populations were generated: CD1a(+) immature DC cultured in the p resence of GM-CSF and IL-4 and mature CD83(+) DC generated by additional st imulation with a cytokine cocktail, Stimulations were performed under serum -free conditions and in the absence of exogenous cytokines. Analysis of T c ell responses showed that mature DC, but not immature DC, were able to indu ce the expansion of syngeneic tumor peptide-specific CD8(+) T cells, Primin g of CD8(+) T cells with peptide-pulsed mature DC rapidly increased the fre quency of antigen-specific T cells (ELISPOT technique). T cells induced by mature DC showed strong antigen-specific cytotoxicity in Cr-51-release assa ys whereas no antigen-specific cytotoxicity was detectable in CTL generated by immature DC. These data show that terminally differentiated mature DC a re necessary for the induction of tumor antigen-specific CTL responses.