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Molecular signatures of Dengue virus-specific IL-10/IFN-γ co-producing CD4 T cells and their association with Dengue disease

Molecular signatures of Dengue virus-specific IL-10/IFN-γ co-producing CD4 T cells and their association with Dengue disease
Molecular signatures of Dengue virus-specific IL-10/IFN-γ co-producing CD4 T cells and their association with Dengue disease

Dengue virus (DENV) can cause diseases ranging from dengue fever (DF) to more severe dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Whether antiviral T cells contribute to the protection against or pathogenesis of severe disease is not well defined. Here, we identified antigen-specific IL-10+IFN-γ+ double-positive (DP) CD4 T cells during acute DENV infection. While the transcriptomic signatures of DP cells partially overlapped with those of cytotoxic and type 1 regulatory CD4 T cells, the majority of them were non-cytotoxic/Tr1 and included IL21IL22CD109, and CCR1. Although we observed a higher frequency of DP cells in DHF, the transcriptomic profile of DP cells was similar in DF and DHF, suggesting that DHF is not associated with the altered phenotypic or functional attributes of DP cells. Overall, this study revealed a DENV-specific DP cell subset in patients with acute dengue disease and argues against altered DP cells as a determinant of DHF.

acute dengue, CD4 T cell, CyTOF, dengue fever, dengue hemorrhagic fever, dengue virus, IFN-γ, IL-10, RNA-seq, transcriptomics
2211-1247
4482-4495.e4
Tian, Yuan
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Seumois, Grégory
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De-Oliveira-Pinto, Luzia M.
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Mateus, Jose
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Herrera-de la Mata, Sara
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Kim, Cheryl
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Hinz, Denise
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Goonawardhana, N. D.Suraj
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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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Balmaseda, Angel
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Grifoni, Alba
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Vijayanand, Pandurangan
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Harris, Eva
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Peters, Bjoern
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Sette, Alessandro
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Weiskopf, Daniela
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Tian, Yuan
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Seumois, Grégory
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De-Oliveira-Pinto, Luzia M.
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Mateus, Jose
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Herrera-de la Mata, Sara
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Kim, Cheryl
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Hinz, Denise
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Goonawardhana, N. D.Suraj
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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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Balmaseda, Angel
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Grifoni, Alba
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Vijayanand, Pandurangan
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Harris, Eva
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Peters, Bjoern
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Sette, Alessandro
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Weiskopf, Daniela
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Tian, Yuan, Seumois, Grégory, De-Oliveira-Pinto, Luzia M., Mateus, Jose, Herrera-de la Mata, Sara, Kim, Cheryl, Hinz, Denise, Goonawardhana, N. D.Suraj, de Silva, Aruna D., Premawansa, Sunil, Premawansa, Gayani, Wijewickrama, Ananda, Balmaseda, Angel, Grifoni, Alba, Vijayanand, Pandurangan, Harris, Eva, Peters, Bjoern, Sette, Alessandro and Weiskopf, Daniela (2019) Molecular signatures of Dengue virus-specific IL-10/IFN-γ co-producing CD4 T cells and their association with Dengue disease. Cell Reports, 29 (13), 4482-4495.e4. (doi:10.1016/j.celrep.2019.11.098).

Record type: Article

Abstract

Dengue virus (DENV) can cause diseases ranging from dengue fever (DF) to more severe dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Whether antiviral T cells contribute to the protection against or pathogenesis of severe disease is not well defined. Here, we identified antigen-specific IL-10+IFN-γ+ double-positive (DP) CD4 T cells during acute DENV infection. While the transcriptomic signatures of DP cells partially overlapped with those of cytotoxic and type 1 regulatory CD4 T cells, the majority of them were non-cytotoxic/Tr1 and included IL21IL22CD109, and CCR1. Although we observed a higher frequency of DP cells in DHF, the transcriptomic profile of DP cells was similar in DF and DHF, suggesting that DHF is not associated with the altered phenotypic or functional attributes of DP cells. Overall, this study revealed a DENV-specific DP cell subset in patients with acute dengue disease and argues against altered DP cells as a determinant of DHF.

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Accepted/In Press date: 22 November 2019
e-pub ahead of print date: 24 December 2019
Published date: 24 December 2019
Keywords: acute dengue, CD4 T cell, CyTOF, dengue fever, dengue hemorrhagic fever, dengue virus, IFN-γ, IL-10, RNA-seq, transcriptomics

Identifiers

Local EPrints ID: 436974
URI: http://eprints.soton.ac.uk/id/eprint/436974
ISSN: 2211-1247
PURE UUID: 88eeed76-dc3b-4d05-a7c9-35ac4cdedc34
ORCID for Pandurangan Vijayanand: ORCID iD orcid.org/0000-0001-7067-9723

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Date deposited: 14 Jan 2020 18:33
Last modified: 05 Jun 2024 19:32

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Contributors

Author: Yuan Tian
Author: Grégory Seumois
Author: Luzia M. De-Oliveira-Pinto
Author: Jose Mateus
Author: Sara Herrera-de la Mata
Author: Cheryl Kim
Author: Denise Hinz
Author: N. D.Suraj Goonawardhana
Author: Aruna D. de Silva
Author: Sunil Premawansa
Author: Gayani Premawansa
Author: Ananda Wijewickrama
Author: Angel Balmaseda
Author: Alba Grifoni
Author: Pandurangan Vijayanand ORCID iD
Author: Eva Harris
Author: Bjoern Peters
Author: Alessandro Sette
Author: Daniela Weiskopf

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