Molecular Signatures of Dengue Virus-Specific IL-10/IFN-γ Co-producing CD4 T Cells and Their Association with Dengue Disease

Summary: 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-sp...

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Main Authors: Yuan Tian, Grégory Seumois, Luzia M. De-Oliveira-Pinto, Jose Mateus, Sara Herrera-de la Mata, Cheryl Kim, Denise Hinz, N.D. Suraj Goonawardhana, Aruna D. de Silva, Sunil Premawansa, Gayani Premawansa, Ananda Wijewickrama, Angel Balmaseda, Alba Grifoni, Pandurangan Vijayanand, Eva Harris, Bjoern Peters, Alessandro Sette, Daniela Weiskopf
Format: Article
Language:English
Published: Elsevier 2019-12-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124719315980
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author Yuan Tian
Grégory Seumois
Luzia M. De-Oliveira-Pinto
Jose Mateus
Sara Herrera-de la Mata
Cheryl Kim
Denise Hinz
N.D. Suraj Goonawardhana
Aruna D. de Silva
Sunil Premawansa
Gayani Premawansa
Ananda Wijewickrama
Angel Balmaseda
Alba Grifoni
Pandurangan Vijayanand
Eva Harris
Bjoern Peters
Alessandro Sette
Daniela Weiskopf
author_facet Yuan Tian
Grégory Seumois
Luzia M. De-Oliveira-Pinto
Jose Mateus
Sara Herrera-de la Mata
Cheryl Kim
Denise Hinz
N.D. Suraj Goonawardhana
Aruna D. de Silva
Sunil Premawansa
Gayani Premawansa
Ananda Wijewickrama
Angel Balmaseda
Alba Grifoni
Pandurangan Vijayanand
Eva Harris
Bjoern Peters
Alessandro Sette
Daniela Weiskopf
author_sort Yuan Tian
collection DOAJ
description Summary: 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 IL21, IL22, CD109, 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. : Tian et al. identify and characterize antigen-specific IL-10+IFN-γ+ double-positive (DP) CD4 T cells in acute dengue patients. DP cells display similar transcriptomic profiles in mild DF and severe DHF, despite their increased frequency in DHF, suggesting that DHF is not associated with the altered phenotype or functionality of DP cells. Keywords: dengue virus, dengue fever, dengue hemorrhagic fever, CD4 T cell, IL-10, IFN-γ, RNA-seq, CyTOF, acute dengue, transcriptomics
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spelling doaj.art-7c7e6719670c412ab9f19874147526162022-12-22T03:53:50ZengElsevierCell Reports2211-12472019-12-01291344824495.e4Molecular Signatures of Dengue Virus-Specific IL-10/IFN-γ Co-producing CD4 T Cells and Their Association with Dengue DiseaseYuan Tian0Grégory Seumois1Luzia M. De-Oliveira-Pinto2Jose Mateus3Sara Herrera-de la Mata4Cheryl Kim5Denise Hinz6N.D. Suraj Goonawardhana7Aruna D. de Silva8Sunil Premawansa9Gayani Premawansa10Ananda Wijewickrama11Angel Balmaseda12Alba Grifoni13Pandurangan Vijayanand14Eva Harris15Bjoern Peters16Alessandro Sette17Daniela Weiskopf18Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USA; Corresponding authorDivision of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USADivision of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USADivision of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USADivision of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USAFlow Cytometry Core Facility, La Jolla Institute for Immunology, La Jolla, CA 92037, USAFlow Cytometry Core Facility, La Jolla Institute for Immunology, La Jolla, CA 92037, USADepartment of Paraclinical Sciences, General Sir John Kotelawala Defense University, Ratmalana 10390, Sri LankaDivision of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USA; Department of Paraclinical Sciences, General Sir John Kotelawala Defense University, Ratmalana 10390, Sri LankaDepartment of Zoology and Environment Sciences, Faculty of Science, University of Colombo, Colombo 00300, Sri LankaNorth Colombo Teaching Hospital, Ragama 11010, Sri LankaNational Institute of Infectious Diseases, Gothatuwa, Angoda 10620, Sri LankaLaboratorio Nacional de Virología, Centro Nacional de Diagnóstico y Referencia, Ministerio de Salud, Managua 16064, NicaraguaDivision of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USADivision of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USADivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA 94720, USADivision of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USA; Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USADivision of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USA; Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USADivision of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USASummary: 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 IL21, IL22, CD109, 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. : Tian et al. identify and characterize antigen-specific IL-10+IFN-γ+ double-positive (DP) CD4 T cells in acute dengue patients. DP cells display similar transcriptomic profiles in mild DF and severe DHF, despite their increased frequency in DHF, suggesting that DHF is not associated with the altered phenotype or functionality of DP cells. Keywords: dengue virus, dengue fever, dengue hemorrhagic fever, CD4 T cell, IL-10, IFN-γ, RNA-seq, CyTOF, acute dengue, transcriptomicshttp://www.sciencedirect.com/science/article/pii/S2211124719315980
spellingShingle Yuan Tian
Grégory Seumois
Luzia M. De-Oliveira-Pinto
Jose Mateus
Sara Herrera-de la Mata
Cheryl Kim
Denise Hinz
N.D. Suraj Goonawardhana
Aruna D. de Silva
Sunil Premawansa
Gayani Premawansa
Ananda Wijewickrama
Angel Balmaseda
Alba Grifoni
Pandurangan Vijayanand
Eva Harris
Bjoern Peters
Alessandro Sette
Daniela Weiskopf
Molecular Signatures of Dengue Virus-Specific IL-10/IFN-γ Co-producing CD4 T Cells and Their Association with Dengue Disease
Cell Reports
title Molecular Signatures of Dengue Virus-Specific IL-10/IFN-γ Co-producing CD4 T Cells and Their Association with Dengue Disease
title_full Molecular Signatures of Dengue Virus-Specific IL-10/IFN-γ Co-producing CD4 T Cells and Their Association with Dengue Disease
title_fullStr Molecular Signatures of Dengue Virus-Specific IL-10/IFN-γ Co-producing CD4 T Cells and Their Association with Dengue Disease
title_full_unstemmed Molecular Signatures of Dengue Virus-Specific IL-10/IFN-γ Co-producing CD4 T Cells and Their Association with Dengue Disease
title_short Molecular Signatures of Dengue Virus-Specific IL-10/IFN-γ Co-producing CD4 T Cells and Their Association with Dengue Disease
title_sort molecular signatures of dengue virus specific il 10 ifn γ co producing cd4 t cells and their association with dengue disease
url http://www.sciencedirect.com/science/article/pii/S2211124719315980
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