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Acute effects of FLT3L treatment on T cells in intact mice

Peripheral T cells express a diverse repertoire of antigen-specific receptors, which together protect against the full range of pathogens. In this context, the total repertoire of memory T cells which are maintained by trophic signals, long after pathogen clearance, is critical. Since these trophic...

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Autores principales: Wolf, Gideon, Gerber, Allison N., Fasana, Zachary G., Rosenberg, Kenneth, Singh, Nevil J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9662129/
https://www.ncbi.nlm.nih.gov/pubmed/36376544
http://dx.doi.org/10.1038/s41598-022-24126-4
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author Wolf, Gideon
Gerber, Allison N.
Fasana, Zachary G.
Rosenberg, Kenneth
Singh, Nevil J.
author_facet Wolf, Gideon
Gerber, Allison N.
Fasana, Zachary G.
Rosenberg, Kenneth
Singh, Nevil J.
author_sort Wolf, Gideon
collection PubMed
description Peripheral T cells express a diverse repertoire of antigen-specific receptors, which together protect against the full range of pathogens. In this context, the total repertoire of memory T cells which are maintained by trophic signals, long after pathogen clearance, is critical. Since these trophic factors include cytokines and self-peptide-MHC, both of which are available from endogenous antigen-presenting cells (APC), we hypothesized that enhancing APC numbers in vivo can be a viable strategy to amplify the population of memory T cells. We evaluated this by acutely treating intact mice with FMS-like tyrosine kinase 3 ligand (Flt3l), which promotes expansion of APCs. Here we report that this treatment allowed for, an expansion of effector-memory CD4+ and CD8+ T cells as well as an increase in their expression of KLRG1 and CD25. In the lymph nodes and spleen, the expansion was limited to a specific CD8 (CD44-low but CD62L−) subset. Functionally, this subset is distinct from naïve T cells and could produce significant amounts of effector cytokines upon restimulation. Taken together, these data suggest that the administration of Flt3L can impact both APC turnover as well as a corresponding flux of specific subsets of CD8+ T cells in an intact peripheral immune compartment.
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spelling pubmed-96621292022-11-14 Acute effects of FLT3L treatment on T cells in intact mice Wolf, Gideon Gerber, Allison N. Fasana, Zachary G. Rosenberg, Kenneth Singh, Nevil J. Sci Rep Article Peripheral T cells express a diverse repertoire of antigen-specific receptors, which together protect against the full range of pathogens. In this context, the total repertoire of memory T cells which are maintained by trophic signals, long after pathogen clearance, is critical. Since these trophic factors include cytokines and self-peptide-MHC, both of which are available from endogenous antigen-presenting cells (APC), we hypothesized that enhancing APC numbers in vivo can be a viable strategy to amplify the population of memory T cells. We evaluated this by acutely treating intact mice with FMS-like tyrosine kinase 3 ligand (Flt3l), which promotes expansion of APCs. Here we report that this treatment allowed for, an expansion of effector-memory CD4+ and CD8+ T cells as well as an increase in their expression of KLRG1 and CD25. In the lymph nodes and spleen, the expansion was limited to a specific CD8 (CD44-low but CD62L−) subset. Functionally, this subset is distinct from naïve T cells and could produce significant amounts of effector cytokines upon restimulation. Taken together, these data suggest that the administration of Flt3L can impact both APC turnover as well as a corresponding flux of specific subsets of CD8+ T cells in an intact peripheral immune compartment. Nature Publishing Group UK 2022-11-14 /pmc/articles/PMC9662129/ /pubmed/36376544 http://dx.doi.org/10.1038/s41598-022-24126-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Wolf, Gideon
Gerber, Allison N.
Fasana, Zachary G.
Rosenberg, Kenneth
Singh, Nevil J.
Acute effects of FLT3L treatment on T cells in intact mice
title Acute effects of FLT3L treatment on T cells in intact mice
title_full Acute effects of FLT3L treatment on T cells in intact mice
title_fullStr Acute effects of FLT3L treatment on T cells in intact mice
title_full_unstemmed Acute effects of FLT3L treatment on T cells in intact mice
title_short Acute effects of FLT3L treatment on T cells in intact mice
title_sort acute effects of flt3l treatment on t cells in intact mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9662129/
https://www.ncbi.nlm.nih.gov/pubmed/36376544
http://dx.doi.org/10.1038/s41598-022-24126-4
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