Prolonged antigen expression following DNA vaccination impairs effector CD8(+) T cell function and memory development
Prolonged antigen expression following DNA vaccination impairs effector CD8(+) T cell function and memory development
After priming, naive T cells undergo a program of expansion, contraction, and memory formation. Numerous studies have indicated that only a brief period of antigenic stimulation is required to fully commit CD8(+) T cells to this program. Nonetheless, the persistence of Ag may modulate the eventual fate of CD8(+) T cells. Using DNA delivery, we showed previously that direct presentation primes high levels of effector CD8(+) T cells as compared with cross-presentation. One explanation now revealed is that prolonged cross-presentation limits effector cell expansion and function. To analyze this, we used a drug-responsive system to regulate Ag expression after DNA injection. Reducing expression to a single burst expanded greater numbers of peptide-specific effector CD8(+) T cells than sustained Ag. Consequences for memory development were assessed after boosting and showed that, although persistent Ag maintained higher numbers of tetramer-positive CD8(+) T cells, these expanded less (similar to 4-fold) than those induced by transient Ag expression (similar to 35-fold). Transient expression at priming therefore led to a net higher secondary response. In terms of vaccine design, we propose that the most effective DNA-based CD8(+) T cell vaccines will be those that deliver a short burst of Ag.
vaccines, responses, cells, dna, persistence, receptor, stimulation, time, single, activation, gene-transfer, development, immunity, cell, t-cells, t-cell, vaccine, secondary, vaccination, expansion, t cells, in-vivo, antigen, cross-presentation, expression, chronic viral-infection
8313-8321
Radcliffe, Joanna N.
95bba459-28f5-46d5-b1f1-8e077f115e52
Roddick, Joanne S.
dddd0a9c-ef7a-4cb4-810d-8927ff1ce76f
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Thirdborough, Stephen M.
161784fb-c8e3-4beb-86b1-cd8bc8ddf8de
2007
Radcliffe, Joanna N.
95bba459-28f5-46d5-b1f1-8e077f115e52
Roddick, Joanne S.
dddd0a9c-ef7a-4cb4-810d-8927ff1ce76f
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Thirdborough, Stephen M.
161784fb-c8e3-4beb-86b1-cd8bc8ddf8de
Radcliffe, Joanna N., Roddick, Joanne S., Stevenson, Freda K. and Thirdborough, Stephen M.
(2007)
Prolonged antigen expression following DNA vaccination impairs effector CD8(+) T cell function and memory development.
Journal of Immunology, 179 (12), .
Abstract
After priming, naive T cells undergo a program of expansion, contraction, and memory formation. Numerous studies have indicated that only a brief period of antigenic stimulation is required to fully commit CD8(+) T cells to this program. Nonetheless, the persistence of Ag may modulate the eventual fate of CD8(+) T cells. Using DNA delivery, we showed previously that direct presentation primes high levels of effector CD8(+) T cells as compared with cross-presentation. One explanation now revealed is that prolonged cross-presentation limits effector cell expansion and function. To analyze this, we used a drug-responsive system to regulate Ag expression after DNA injection. Reducing expression to a single burst expanded greater numbers of peptide-specific effector CD8(+) T cells than sustained Ag. Consequences for memory development were assessed after boosting and showed that, although persistent Ag maintained higher numbers of tetramer-positive CD8(+) T cells, these expanded less (similar to 4-fold) than those induced by transient Ag expression (similar to 35-fold). Transient expression at priming therefore led to a net higher secondary response. In terms of vaccine design, we propose that the most effective DNA-based CD8(+) T cell vaccines will be those that deliver a short burst of Ag.
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Published date: 2007
Keywords:
vaccines, responses, cells, dna, persistence, receptor, stimulation, time, single, activation, gene-transfer, development, immunity, cell, t-cells, t-cell, vaccine, secondary, vaccination, expansion, t cells, in-vivo, antigen, cross-presentation, expression, chronic viral-infection
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Local EPrints ID: 62888
URI: http://eprints.soton.ac.uk/id/eprint/62888
ISSN: 0022-1767
PURE UUID: df50bf73-1811-498f-9e96-f88b754d37f4
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Date deposited: 05 Sep 2008
Last modified: 23 Jul 2022 01:41
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Author:
Joanna N. Radcliffe
Author:
Joanne S. Roddick
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