Long-lived memory CD8+ T cells are programmed by prolonged antigen exposure and low levels of cellular activation.

CD8+ T cells play a crucial role in controlling intracellular pathogens. The level of memory CD8+ T cells developing after vaccination or infection influences the degree of T cell-mediated protection after secondary infection. We used defined animal models and infections/immunizations by replicating...

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Main Authors: Bachmann, M, Beerli, R, Agnellini, P, Wolint, P, Schwarz, K, Oxenius, A
Format: Journal article
Language:English
Published: 2006
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author Bachmann, M
Beerli, R
Agnellini, P
Wolint, P
Schwarz, K
Oxenius, A
author_facet Bachmann, M
Beerli, R
Agnellini, P
Wolint, P
Schwarz, K
Oxenius, A
author_sort Bachmann, M
collection OXFORD
description CD8+ T cells play a crucial role in controlling intracellular pathogens. The level of memory CD8+ T cells developing after vaccination or infection influences the degree of T cell-mediated protection after secondary infection. We used defined animal models and infections/immunizations by replicating or non-replicating antigens to define on a molecular and cellular level in vivo the parameters that identify and shape long-lived CD8+ T cell memory. We show that the timing of antigen exposure during vaccination is key for the induction of long-lived T cell memory. Brief antigen exposure induced high numbers of effector cells but limited development of long-lived CD8+ memory T cells. In contrast, prolonged antigen exposure for up to 9 days induced similar numbers of effector T cells but additionally resulted in high levels of memory CD8+ T cells. Unexpectedly CD127 (IL-7Ralpha) expression on CD8+ T cells during the acute priming phase was a necessary but not sufficient requirement for entering the pool of long-lived antigen-independent memory CD8+ T cells. However, we provide strong evidence for the interpretation that programming of long-lived memory T cells was driven by low levels of transcription factor eomesodermin and protease inhibitor Spi2A as well as reduced phosphorylation of c-JUN.
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spelling oxford-uuid:e85cdc18-058c-4290-95fc-f04f77572e422022-03-27T10:46:03ZLong-lived memory CD8+ T cells are programmed by prolonged antigen exposure and low levels of cellular activation.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e85cdc18-058c-4290-95fc-f04f77572e42EnglishSymplectic Elements at Oxford2006Bachmann, MBeerli, RAgnellini, PWolint, PSchwarz, KOxenius, ACD8+ T cells play a crucial role in controlling intracellular pathogens. The level of memory CD8+ T cells developing after vaccination or infection influences the degree of T cell-mediated protection after secondary infection. We used defined animal models and infections/immunizations by replicating or non-replicating antigens to define on a molecular and cellular level in vivo the parameters that identify and shape long-lived CD8+ T cell memory. We show that the timing of antigen exposure during vaccination is key for the induction of long-lived T cell memory. Brief antigen exposure induced high numbers of effector cells but limited development of long-lived CD8+ memory T cells. In contrast, prolonged antigen exposure for up to 9 days induced similar numbers of effector T cells but additionally resulted in high levels of memory CD8+ T cells. Unexpectedly CD127 (IL-7Ralpha) expression on CD8+ T cells during the acute priming phase was a necessary but not sufficient requirement for entering the pool of long-lived antigen-independent memory CD8+ T cells. However, we provide strong evidence for the interpretation that programming of long-lived memory T cells was driven by low levels of transcription factor eomesodermin and protease inhibitor Spi2A as well as reduced phosphorylation of c-JUN.
spellingShingle Bachmann, M
Beerli, R
Agnellini, P
Wolint, P
Schwarz, K
Oxenius, A
Long-lived memory CD8+ T cells are programmed by prolonged antigen exposure and low levels of cellular activation.
title Long-lived memory CD8+ T cells are programmed by prolonged antigen exposure and low levels of cellular activation.
title_full Long-lived memory CD8+ T cells are programmed by prolonged antigen exposure and low levels of cellular activation.
title_fullStr Long-lived memory CD8+ T cells are programmed by prolonged antigen exposure and low levels of cellular activation.
title_full_unstemmed Long-lived memory CD8+ T cells are programmed by prolonged antigen exposure and low levels of cellular activation.
title_short Long-lived memory CD8+ T cells are programmed by prolonged antigen exposure and low levels of cellular activation.
title_sort long lived memory cd8 t cells are programmed by prolonged antigen exposure and low levels of cellular activation
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