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Unique phenotypes and clonal expansions of human CD4 effector memory T cells re-expressing CD45RA

Unique phenotypes and clonal expansions of human CD4 effector memory T cells re-expressing CD45RA
Unique phenotypes and clonal expansions of human CD4 effector memory T cells re-expressing CD45RA

The expression of CD45RA is generally associated with naive T cells. However, a subset of effector memory T cells re-expresses CD45RA (termed TEMRA) after antigenic stimulation with unknown molecular characteristics and functions. CD4 TEMRA cells have been implicated in protective immunity against pathogens such as dengue virus (DENV). Here we show that not only the frequency but also the phenotype of CD4 TEMRA cells are heterogeneous between individuals. These cells can be subdivided into two major subsets based on the expression of the adhesion G protein-coupled receptor GPR56, and GPR56+ TEMRA cells display a transcriptional and proteomic program with cytotoxic features that is distinct from effector memory T cells. Moreover, GPR56+ TEMRA cells have higher levels of clonal expansion and contain the majority of virus-specific TEMRA cells. Overall, this study reveals the heterogeneity of CD4 TEMRA cells and provides insights into T-cell responses against DENV and other viral pathogens.

Journal Article
1473
Tian, Yuan
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Babor, Mariana
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Lane, Jerome
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Schulten, Veronique
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Patil, Veena S
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Seumois, Grégory
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Rosales, Sandy L
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Fu, Zheng
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Picarda, Gaelle
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Burel, Julie
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Zapardiel-Gonzalo, Jose
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Tennekoon, Rashika N.
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De Silva, Aruna D.
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Premawansa, Sunil
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Premawansa, Gayani
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Wijewickrama, Ananda
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Greenbaum, Jason A.
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Vijayanand, Pandurangan
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Weiskopf, Daniela
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Sette, Alessandro
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Peters, Bjoern
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Tian, Yuan
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Babor, Mariana
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Lane, Jerome
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Schulten, Veronique
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Patil, Veena S
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Seumois, Grégory
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Rosales, Sandy L
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Fu, Zheng
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Picarda, Gaelle
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Burel, Julie
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Zapardiel-Gonzalo, Jose
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Tennekoon, Rashika N.
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De Silva, Aruna D.
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Premawansa, Sunil
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Premawansa, Gayani
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Wijewickrama, Ananda
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Greenbaum, Jason A.
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Vijayanand, Pandurangan
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Weiskopf, Daniela
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Sette, Alessandro
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Peters, Bjoern
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Tian, Yuan, Babor, Mariana, Lane, Jerome, Schulten, Veronique, Patil, Veena S, Seumois, Grégory, Rosales, Sandy L, Fu, Zheng, Picarda, Gaelle, Burel, Julie, Zapardiel-Gonzalo, Jose, Tennekoon, Rashika N., De Silva, Aruna D., Premawansa, Sunil, Premawansa, Gayani, Wijewickrama, Ananda, Greenbaum, Jason A., Vijayanand, Pandurangan, Weiskopf, Daniela, Sette, Alessandro and Peters, Bjoern (2017) Unique phenotypes and clonal expansions of human CD4 effector memory T cells re-expressing CD45RA. Nature Communications, 8 (1), 1473. (doi:10.1038/s41467-017-01728-5).

Record type: Article

Abstract

The expression of CD45RA is generally associated with naive T cells. However, a subset of effector memory T cells re-expresses CD45RA (termed TEMRA) after antigenic stimulation with unknown molecular characteristics and functions. CD4 TEMRA cells have been implicated in protective immunity against pathogens such as dengue virus (DENV). Here we show that not only the frequency but also the phenotype of CD4 TEMRA cells are heterogeneous between individuals. These cells can be subdivided into two major subsets based on the expression of the adhesion G protein-coupled receptor GPR56, and GPR56+ TEMRA cells display a transcriptional and proteomic program with cytotoxic features that is distinct from effector memory T cells. Moreover, GPR56+ TEMRA cells have higher levels of clonal expansion and contain the majority of virus-specific TEMRA cells. Overall, this study reveals the heterogeneity of CD4 TEMRA cells and provides insights into T-cell responses against DENV and other viral pathogens.

Text
s41467-017-01728-5 - Version of Record
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e-pub ahead of print date: 13 November 2017
Published date: 13 November 2017
Keywords: Journal Article

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Local EPrints ID: 422638
URI: https://eprints.soton.ac.uk/id/eprint/422638
PURE UUID: 13136b5c-bc8e-49b6-9c92-798a574096ba

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Date deposited: 27 Jul 2018 16:30
Last modified: 02 Dec 2019 18:02

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Contributors

Author: Yuan Tian
Author: Mariana Babor
Author: Jerome Lane
Author: Veronique Schulten
Author: Veena S Patil
Author: Grégory Seumois
Author: Sandy L Rosales
Author: Zheng Fu
Author: Gaelle Picarda
Author: Julie Burel
Author: Jose Zapardiel-Gonzalo
Author: Rashika N. Tennekoon
Author: Aruna D. De Silva
Author: Sunil Premawansa
Author: Gayani Premawansa
Author: Ananda Wijewickrama
Author: Jason A. Greenbaum
Author: Pandurangan Vijayanand
Author: Daniela Weiskopf
Author: Alessandro Sette
Author: Bjoern Peters

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