Mature dendritic cells boost functionally superior CD8(+) T-cell without foreign helper epitopes

We have recently shown that a single injection of mature, antigen-pulsed, h uman dendritic cells (DCs) rapidly elicits CD4(+) and CD8(+) T-cell immunit y in vivo. The DCs were pulsed with 2 foreign proteins, keyhole limpet hemo cyanin (KLH) and tetanus toroid (TT), as well as an HLA A2.1-restricted inf luenza matrix peptide (MP). Responses to all 3 antigens peaked at 30-90 day s after immunization and declined thereafter. To determine if the foreign h elper proteins (TT and KLH) were essential for CD8(+) T-cell responses to t he viral peptide, we reinjected 3 of the HLA-2.1 subjects with mature DCs p ulsed with MP alone. All 3 volunteers showed a rapid boost in MP-specific i mmunity, and freshly sampled blood from 1 contained cytolytic T cells. In a ll 3 subjects, CD8(+) T-cell responses to booster DCs were faster and of gr eater magnitude than the responses to the first DC injection. Importantly, the T cells that proliferated after booster DC treatment secreted interfero n-gamma upon challenge with much lower doses of viral peptide than those el icited after the first injection, indicating a higher functional avidity fo r the ligand. These data begin to outline the kinetics of T-cell immunity i n response to DCs and demonstrate that booster injections of mature DCs enh ance both qualitative and quantitative aspects of CD8(+) T-cell function in humans.