Rapid generation of broad T-cell immunity in humans after a single injection of mature dendritic cells

Dendritic cells (DCs) are potent antigen-presenting cells that initiate pro tective T-cell immunity in mice. To study the immunogenicity of DCs in huma ns, we injected 9 healthy subjects subcutaneously with a control injection of autologous monocyte-derived, mature DCs, followed 4-6 weeks later by DCs pulsed with keyhole limpet hemocyanin (KLH), HLA-A*0201-positive restricte d influenza matrix peptide (MP), and tetanus toroid (TT). Four more subject s received these antigens without DCs. Injection of unpulsed DCs, or antige ns alone, failed to immunize. Priming of CD4(+) T cells to KLH was observed in all 9 subjects injected with KLH-pulsed DCs, and boosting of TT-specifi c T-cell immunity was seen in 5 of 6 subjects injected with TT-pulsed DCs. Injection of antigen-pulsed DCs led to a severalfold increase in freshly is olated MP-specific, IFN-gamma-secreting CD8(+) T cells in all 6 HLA-A*0201- positive subjects, as early as 7 days after injection. When T cells were bo osted in culture, there was an increase in MHC tetramer-binding cells and c ytotoxic T cells after DC vaccination. These data provide the first control led evidence of the immunogenicity of DCs in humans, and demonstrate that a single injection of mature DCs rapidly expands T-cell immunity.