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...
Main Authors: | , , , , , |
---|---|
Format: | Journal article |
Language: | English |
Published: |
2006
|
_version_ | 1826302561909473280 |
---|---|
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. |
first_indexed | 2024-03-07T05:49:27Z |
format | Journal article |
id | oxford-uuid:e85cdc18-058c-4290-95fc-f04f77572e42 |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-07T05:49:27Z |
publishDate | 2006 |
record_format | dspace |
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 |
work_keys_str_mv | AT bachmannm longlivedmemorycd8tcellsareprogrammedbyprolongedantigenexposureandlowlevelsofcellularactivation AT beerlir longlivedmemorycd8tcellsareprogrammedbyprolongedantigenexposureandlowlevelsofcellularactivation AT agnellinip longlivedmemorycd8tcellsareprogrammedbyprolongedantigenexposureandlowlevelsofcellularactivation AT wolintp longlivedmemorycd8tcellsareprogrammedbyprolongedantigenexposureandlowlevelsofcellularactivation AT schwarzk longlivedmemorycd8tcellsareprogrammedbyprolongedantigenexposureandlowlevelsofcellularactivation AT oxeniusa longlivedmemorycd8tcellsareprogrammedbyprolongedantigenexposureandlowlevelsofcellularactivation |