Early priming minimizes the age-related immune compromise of CD8⁺ T cell diversity and function.

The elderly are particularly susceptible to influenza A virus infections, with increased occurrence, disease severity and reduced vaccine efficacy attributed to declining immunity. Experimentally, the age-dependent decline in influenza-specific CD8(+) T cell responsiveness reflects both functional c...

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Autores principales:	Sophie A Valkenburg, Vanessa Venturi, Thurston H Y Dang, Nicola L Bird, Peter C Doherty, Stephen J Turner, Miles P Davenport, Katherine Kedzierska
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/6fa5a2ce4ae94b5194f76687d579ccd1
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spelling	oai:doaj.org-article:6fa5a2ce4ae94b5194f76687d579ccd12021-11-18T06:04:44ZEarly priming minimizes the age-related immune compromise of CD8⁺ T cell diversity and function.1553-73661553-737410.1371/journal.ppat.1002544https://doaj.org/article/6fa5a2ce4ae94b5194f76687d579ccd12012-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22383879/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374The elderly are particularly susceptible to influenza A virus infections, with increased occurrence, disease severity and reduced vaccine efficacy attributed to declining immunity. Experimentally, the age-dependent decline in influenza-specific CD8(+) T cell responsiveness reflects both functional compromise and the emergence of 'repertoire holes' arising from the loss of low frequency clonotypes. In this study, we asked whether early priming limits the time-related attrition of immune competence. Though primary responses in aged mice were compromised, animals vaccinated at 6 weeks then challenged >20 months later had T-cell responses that were normal in magnitude. Both functional quality and the persistence of 'preferred' TCR clonotypes that expand in a characteristic immunodominance hierarchy were maintained following early priming. Similar to the early priming, vaccination at 22 months followed by challenge retained a response magnitude equivalent to young mice. However, late priming resulted in reduced TCRβ diversity in comparison with vaccination earlier in life. Thus, early priming was critical to maintaining individual and population-wide TCRβ diversity. In summary, early exposure leads to the long-term maintenance of memory T cells and thus preserves optimal, influenza-specific CD8(+) T-cell responsiveness and protects against the age-related attrition of naïve T-cell precursors. Our study supports development of vaccines that prime CD8(+) T-cells early in life to elicit the broadest possible spectrum of CD8(+) T-cell memory and preserve the magnitude, functionality and TCR usage of responding populations. In addition, our study provides the most comprehensive analysis of the aged (primary, secondary primed-early and secondary primed-late) TCR repertoires published to date.Sophie A ValkenburgVanessa VenturiThurston H Y DangNicola L BirdPeter C DohertyStephen J TurnerMiles P DavenportKatherine KedzierskaPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 2, p e1002544 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Sophie A Valkenburg Vanessa Venturi Thurston H Y Dang Nicola L Bird Peter C Doherty Stephen J Turner Miles P Davenport Katherine Kedzierska Early priming minimizes the age-related immune compromise of CD8⁺ T cell diversity and function.
description	The elderly are particularly susceptible to influenza A virus infections, with increased occurrence, disease severity and reduced vaccine efficacy attributed to declining immunity. Experimentally, the age-dependent decline in influenza-specific CD8(+) T cell responsiveness reflects both functional compromise and the emergence of 'repertoire holes' arising from the loss of low frequency clonotypes. In this study, we asked whether early priming limits the time-related attrition of immune competence. Though primary responses in aged mice were compromised, animals vaccinated at 6 weeks then challenged >20 months later had T-cell responses that were normal in magnitude. Both functional quality and the persistence of 'preferred' TCR clonotypes that expand in a characteristic immunodominance hierarchy were maintained following early priming. Similar to the early priming, vaccination at 22 months followed by challenge retained a response magnitude equivalent to young mice. However, late priming resulted in reduced TCRβ diversity in comparison with vaccination earlier in life. Thus, early priming was critical to maintaining individual and population-wide TCRβ diversity. In summary, early exposure leads to the long-term maintenance of memory T cells and thus preserves optimal, influenza-specific CD8(+) T-cell responsiveness and protects against the age-related attrition of naïve T-cell precursors. Our study supports development of vaccines that prime CD8(+) T-cells early in life to elicit the broadest possible spectrum of CD8(+) T-cell memory and preserve the magnitude, functionality and TCR usage of responding populations. In addition, our study provides the most comprehensive analysis of the aged (primary, secondary primed-early and secondary primed-late) TCR repertoires published to date.
format	article
author	Sophie A Valkenburg Vanessa Venturi Thurston H Y Dang Nicola L Bird Peter C Doherty Stephen J Turner Miles P Davenport Katherine Kedzierska
author_facet	Sophie A Valkenburg Vanessa Venturi Thurston H Y Dang Nicola L Bird Peter C Doherty Stephen J Turner Miles P Davenport Katherine Kedzierska
author_sort	Sophie A Valkenburg
title	Early priming minimizes the age-related immune compromise of CD8⁺ T cell diversity and function.
title_short	Early priming minimizes the age-related immune compromise of CD8⁺ T cell diversity and function.
title_full	Early priming minimizes the age-related immune compromise of CD8⁺ T cell diversity and function.
title_fullStr	Early priming minimizes the age-related immune compromise of CD8⁺ T cell diversity and function.
title_full_unstemmed	Early priming minimizes the age-related immune compromise of CD8⁺ T cell diversity and function.
title_sort	early priming minimizes the age-related immune compromise of cd8⁺ t cell diversity and function.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/6fa5a2ce4ae94b5194f76687d579ccd1
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Early priming minimizes the age-related immune compromise of CD8⁺ T cell diversity and function.

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