Mature dendritic cells boost functionally superior CD8(+) T-cell in humans without foreign helper epitopes.
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-gamma 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.
Dhodapkar
M V
MV
Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, New York 10021, USA. dhodapm@rockvax.rockefeller.edu
Krasovsky
J
J
Steinman
R M
RM
Bhardwaj
N
N
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000276:immunology / Q000502:physiology* / Q000637:transplantation; D004768:Enterotoxins / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D007114:Immunization; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D010446:Peptide Fragments / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology; D014763:Viral Matrix Proteins / Q000276:immunology
D004768:Enterotoxins; D000939:Epitopes; D015789:HLA-A2 Antigen; D010446:Peptide Fragments; D013745:Tetanus Toxoid; D014763:Viral Matrix Proteins; C085077:influenza matrix peptide MAT(17-31); C026066:enterotoxin A, Staphylococcal; D007371:Interferon-gamma; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin