[HTML][HTML] Mature dendritic cells boost functionally superior CD8+ T-cell in humans without foreign helper epitopes

MV Dhodapkar, J Krasovsky… - The Journal of …, 2000 - Am Soc Clin Investig
MV Dhodapkar, J Krasovsky, RM Steinman, N Bhardwaj
The Journal of clinical investigation, 2000Am Soc Clin Investig
We have recently shown that a single injection of mature, antigen-pulsed, human dendritic
cells (DCs) rapidly elicits CD4+ and CD8+ T-cell immunity in vivo. The DCs were pulsed with
2 foreign proteins, keyhole limpet hemocyanin (KLH) and tetanus toxoid (TT), as well as an
HLA A2. 1-restricted influenza matrix peptide (MP). Responses to all 3 antigens peaked at
30–90 days after immunization and declined thereafter. To determine if the foreign helper
proteins (TT and KLH) were essential for CD8+ T-cell responses to the viral peptide, we …
We have recently shown that a single injection of mature, antigen-pulsed, human dendritic cells (DCs) rapidly elicits CD4+ and CD8+ T-cell immunity in vivo. The DCs were pulsed with 2 foreign proteins, keyhole limpet hemocyanin (KLH) and tetanus toxoid (TT), as well as an HLA A2.1-restricted influenza matrix peptide (MP). Responses to all 3 antigens peaked at 30–90 days after immunization and declined thereafter. To determine if the foreign helper proteins (TT and KLH) were essential for CD8+ T-cell responses to the viral peptide, we reinjected 3 of the HLA-2.1 subjects with mature DCs pulsed with MP alone. All 3 volunteers showed a rapid boost in MP-specific immunity, and freshly sampled blood from 1 contained cytolytic T cells. In all 3 subjects, CD8+ T-cell responses to booster DCs were faster and of greater magnitude than the responses to the first DC injection. Importantly, the T cells that proliferated after booster DC treatment secreted interferon-γ upon challenge with much lower doses of viral peptide than those elicited after the first injection, indicating a higher functional avidity for the ligand. These data begin to outline the kinetics of T-cell immunity in response to DCs and demonstrate that booster injections of mature DCs enhance both qualitative and quantitative aspects of CD8+ T-cell function in humans.
This article may have been published online in advance of the print edition. The date of publication is available from the JCI website, http://www.jci.org. J. Clin. Invest.105:R9–R14 (2000).
The Journal of Clinical Investigation