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Jonuleit, H. et al.

Jonuleit, Giesecke, Kandemir, Paragnik, Knop, Enk,

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 cultured DC from HLA-typed volunteers for the induction of tumor peptide-specific CD8+ T cells. The strength and specificity of the resulting CTL responses were investigated. For stimulation of syngeneic CD8+ T cells two well-defined DC populations were generated: CD1a+ immature DC cultured in the presence of GM-CSF and IL-4 and mature CD83+ DC generated by additional stimulation with a cytokine cocktail. Stimulations were performed under serum-free conditions and in the absence of exogenous cytokines. Analysis of T cell responses showed that mature DC, but not immature DC, were able to induce the expansion of syngeneic tumor peptide-specific CD8+ T cells. Priming of CD8+ T cells with peptide-pulsed mature DC rapidly increased the frequency of antigen-specific T cells (ELISPOT technique). T cells induced by mature DC showed strong antigen-specific cytotoxicity in 51Cr-release assays whereas no antigen-specific cytotoxicity was detectable in CTL generated by immature DC. These data show that terminally differentiated mature DC are necessary for the induction of tumor antigen-specific CTL responses.[1]

References

Induction of tumor peptide-specific cytotoxic T cells under serum-free conditions by mature human dendritic cells. Jonuleit, H., Giesecke, A., Kandemir, A., Paragnik, L., Knop, J., Enk, A.H. Arch. Dermatol. Res. (2000) [Pubmed]

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