Dynamics and turnover of memory CD8 T cell responses following yellow fever vaccination.

Understanding how immunological memory lasts a lifetime requires quantifying changes in the number of memory cells as well as how their division and death rates change over time. We address these questions by using a statistically powerful mixed-effects differential equations framework to analyze da...

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Autores principales:	Veronika I Zarnitsyna, Rama S Akondy, Hasan Ahmed, Donald J McGuire, Vladimir G Zarnitsyn, Mia Moore, Philip L F Johnson, Rafi Ahmed, Kelvin W Li, Marc K Hellerstein, Rustom Antia
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/d833a13fe7e34b38b5d1e8330ab10a2f
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spelling	oai:doaj.org-article:d833a13fe7e34b38b5d1e8330ab10a2f2021-12-02T19:57:30ZDynamics and turnover of memory CD8 T cell responses following yellow fever vaccination.1553-734X1553-735810.1371/journal.pcbi.1009468https://doaj.org/article/d833a13fe7e34b38b5d1e8330ab10a2f2021-10-01T00:00:00Zhttps://doi.org/10.1371/journal.pcbi.1009468https://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Understanding how immunological memory lasts a lifetime requires quantifying changes in the number of memory cells as well as how their division and death rates change over time. We address these questions by using a statistically powerful mixed-effects differential equations framework to analyze data from two human studies that follow CD8 T cell responses to the yellow fever vaccine (YFV-17D). Models were first fit to the frequency of YFV-specific memory CD8 T cells and deuterium enrichment in those cells 42 days to 1 year post-vaccination. A different dataset, on the loss of YFV-specific CD8 T cells over three decades, was used to assess out of sample predictions of our models. The commonly used exponential and bi-exponential decline models performed relatively poorly. Models with the cell loss following a power law (exactly or approximately) were most predictive. Notably, using only the first year of data, these models accurately predicted T cell frequencies up to 30 years post-vaccination. Our analyses suggest that division rates of these cells drop and plateau at a low level (0.1% per day, ∼ double the estimated values for naive T cells) within one year following vaccination, whereas death rates continue to decline for much longer. Our results show that power laws can be predictive for T cell memory, a finding that may be useful for vaccine evaluation and epidemiological modeling. Moreover, since power laws asymptotically decline more slowly than any exponential decline, our results help explain the longevity of immune memory phenomenologically.Veronika I ZarnitsynaRama S AkondyHasan AhmedDonald J McGuireVladimir G ZarnitsynMia MoorePhilip L F JohnsonRafi AhmedKelvin W LiMarc K HellersteinRustom AntiaPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 17, Iss 10, p e1009468 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Veronika I Zarnitsyna Rama S Akondy Hasan Ahmed Donald J McGuire Vladimir G Zarnitsyn Mia Moore Philip L F Johnson Rafi Ahmed Kelvin W Li Marc K Hellerstein Rustom Antia Dynamics and turnover of memory CD8 T cell responses following yellow fever vaccination.
description	Understanding how immunological memory lasts a lifetime requires quantifying changes in the number of memory cells as well as how their division and death rates change over time. We address these questions by using a statistically powerful mixed-effects differential equations framework to analyze data from two human studies that follow CD8 T cell responses to the yellow fever vaccine (YFV-17D). Models were first fit to the frequency of YFV-specific memory CD8 T cells and deuterium enrichment in those cells 42 days to 1 year post-vaccination. A different dataset, on the loss of YFV-specific CD8 T cells over three decades, was used to assess out of sample predictions of our models. The commonly used exponential and bi-exponential decline models performed relatively poorly. Models with the cell loss following a power law (exactly or approximately) were most predictive. Notably, using only the first year of data, these models accurately predicted T cell frequencies up to 30 years post-vaccination. Our analyses suggest that division rates of these cells drop and plateau at a low level (0.1% per day, ∼ double the estimated values for naive T cells) within one year following vaccination, whereas death rates continue to decline for much longer. Our results show that power laws can be predictive for T cell memory, a finding that may be useful for vaccine evaluation and epidemiological modeling. Moreover, since power laws asymptotically decline more slowly than any exponential decline, our results help explain the longevity of immune memory phenomenologically.
format	article
author	Veronika I Zarnitsyna Rama S Akondy Hasan Ahmed Donald J McGuire Vladimir G Zarnitsyn Mia Moore Philip L F Johnson Rafi Ahmed Kelvin W Li Marc K Hellerstein Rustom Antia
author_facet	Veronika I Zarnitsyna Rama S Akondy Hasan Ahmed Donald J McGuire Vladimir G Zarnitsyn Mia Moore Philip L F Johnson Rafi Ahmed Kelvin W Li Marc K Hellerstein Rustom Antia
author_sort	Veronika I Zarnitsyna
title	Dynamics and turnover of memory CD8 T cell responses following yellow fever vaccination.
title_short	Dynamics and turnover of memory CD8 T cell responses following yellow fever vaccination.
title_full	Dynamics and turnover of memory CD8 T cell responses following yellow fever vaccination.
title_fullStr	Dynamics and turnover of memory CD8 T cell responses following yellow fever vaccination.
title_full_unstemmed	Dynamics and turnover of memory CD8 T cell responses following yellow fever vaccination.
title_sort	dynamics and turnover of memory cd8 t cell responses following yellow fever vaccination.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/d833a13fe7e34b38b5d1e8330ab10a2f
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_version_	1718375871341920256

Dynamics and turnover of memory CD8 T cell responses following yellow fever vaccination.

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