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 protective T-cell immunity in mice. To study the immunogenicity of DCs in humans, we injected 9 healthy subjects subcutaneously with a control injection of autologous monocyte-derived, mature DCs, followed 4-6 weeks later by DCs...

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Main Authors: Dhodapkar, M, Steinman, R, Sapp, M, Desai, H, Fossella, C, Krasovsky, J, Donahoe, S, Dunbar, P, Cerundolo, V, Nixon, D, Bhardwaj, N
Format: Journal article
Language:English
Published: 1999
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author Dhodapkar, M
Steinman, R
Sapp, M
Desai, H
Fossella, C
Krasovsky, J
Donahoe, S
Dunbar, P
Cerundolo, V
Nixon, D
Bhardwaj, N
author_facet Dhodapkar, M
Steinman, R
Sapp, M
Desai, H
Fossella, C
Krasovsky, J
Donahoe, S
Dunbar, P
Cerundolo, V
Nixon, D
Bhardwaj, N
author_sort Dhodapkar, M
collection OXFORD
description Dendritic cells (DCs) are potent antigen-presenting cells that initiate protective T-cell immunity in mice. To study the immunogenicity of DCs in humans, 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 restricted influenza matrix peptide (MP), and tetanus toxoid (TT). Four more subjects received these antigens without DCs. Injection of unpulsed DCs, or antigens 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-specific 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 isolated 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 boosted in culture, there was an increase in MHC tetramer-binding cells and cytotoxic T cells after DC vaccination. These data provide the first controlled evidence of the immunogenicity of DCs in humans, and demonstrate that a single injection of mature DCs rapidly expands T-cell immunity.
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spelling oxford-uuid:5703d098-f04c-4315-b781-78a7c32adbba2022-03-26T16:54:04ZRapid generation of broad T-cell immunity in humans after a single injection of mature dendritic cells.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5703d098-f04c-4315-b781-78a7c32adbbaEnglishSymplectic Elements at Oxford1999Dhodapkar, MSteinman, RSapp, MDesai, HFossella, CKrasovsky, JDonahoe, SDunbar, PCerundolo, VNixon, DBhardwaj, NDendritic cells (DCs) are potent antigen-presenting cells that initiate protective T-cell immunity in mice. To study the immunogenicity of DCs in humans, 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 restricted influenza matrix peptide (MP), and tetanus toxoid (TT). Four more subjects received these antigens without DCs. Injection of unpulsed DCs, or antigens 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-specific 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 isolated 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 boosted in culture, there was an increase in MHC tetramer-binding cells and cytotoxic T cells after DC vaccination. These data provide the first controlled evidence of the immunogenicity of DCs in humans, and demonstrate that a single injection of mature DCs rapidly expands T-cell immunity.
spellingShingle Dhodapkar, M
Steinman, R
Sapp, M
Desai, H
Fossella, C
Krasovsky, J
Donahoe, S
Dunbar, P
Cerundolo, V
Nixon, D
Bhardwaj, N
Rapid generation of broad T-cell immunity in humans after a single injection of mature dendritic cells.
title Rapid generation of broad T-cell immunity in humans after a single injection of mature dendritic cells.
title_full Rapid generation of broad T-cell immunity in humans after a single injection of mature dendritic cells.
title_fullStr Rapid generation of broad T-cell immunity in humans after a single injection of mature dendritic cells.
title_full_unstemmed Rapid generation of broad T-cell immunity in humans after a single injection of mature dendritic cells.
title_short Rapid generation of broad T-cell immunity in humans after a single injection of mature dendritic cells.
title_sort rapid generation of broad t cell immunity in humans after a single injection of mature dendritic cells
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