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

49 Pages Posted: 21 Aug 2019 Sneak Peek Status: Review Complete

See all articles by Yuan Tian

Yuan Tian

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery

Grégory Seumois

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery

Luzia M. De-Oliveira-Pinto

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery

Sara Herrera-de la Mata

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery

Cheryl Kim

La Jolla Institute for Allergy and Immunology (LIAI) - Flow Cytometry Core Facility

Denise Hinz

La Jolla Institute for Allergy and Immunology (LIAI) - Flow Cytometry Core Facility

N.D. Suraj Goonawardhana

General Sir John Kotelawala Defense University - Department of Paraclinical Sciences

Aruna D. de Silva

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery

Sunil Premawansa

University of Colombo - Department of Zoology and Environment Sciences

Gayani Premawansa

North Colombo Teaching Hospital

Ananda Wijewickrama

National Institute of Infectious Diseases

Angel Balmaseda

Ministry of Health, Nicaragua - National Laboratory of Virology

Alba Grifoni

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery

Pandurangan Vijayanand

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery

Eva Harris

University of California, Berkeley - Division of Infectious Diseases and Vaccinology

Bjoern Peters

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery

Alessandro Sette

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery

Daniela Weiskopf

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery

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Abstract

Dengue virus (DENV) can cause diseases ranging from self-limiting dengue fever (DF) to more severe dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Whether DENV-specific T cells contribute to the protection against or pathogenesis of severe dengue disease is not well defined. In this study, we identified a novel IL-10+IFN-Υ+ double positive (DP) CD4 T cell subset that predominated the antigen-specific CD4 T cell response during acute DENV infection. While some of the transcriptomic and proteomic signatures of DP cells marginally overlapped with previously identified markers of cytotoxic CD4 T cells and type 1 regulatory T (Tr1)-like cell, the vast majority of the genes differentially expressed in DP cells were novel and included genes such as IL21, IL22, CD109, and CCR1. Although we observed higher frequencies of DENV-specific DP cells in DHF patients than in DF patients, their transcriptomic profile was similar in these two groups of patients, suggesting that dengue disease severity is not associated with altered phenotypic or functional attributes of this novel CD4 T cell subset. Overall, our in-depth transcriptomic, phenotypic, and functional analyses revealed a novel DENV-specific DP cell subset in patients with acute dengue disease and argue against altered CD4 T cell response as a determinant of disease severity.

Keywords: Dengue virus, Dengue fever, Dengue hemorrhagic fever, CD4 T cell, IL-10, IFN-γ, RNA-seq, CyTOF

Suggested Citation

Tian, Yuan and Seumois, Grégory and De-Oliveira-Pinto, Luzia M. and Herrera-de la Mata, Sara and Kim, Cheryl and Hinz, Denise and Goonawardhana, N.D. Suraj and de Silva, Aruna D. and Premawansa, Sunil and Premawansa, Gayani and Wijewickrama, Ananda and Balmaseda, Angel and Grifoni, Alba and Vijayanand, Pandurangan and Harris, Eva and Peters, Bjoern and Sette, Alessandro and Weiskopf, Daniela, Molecular Signatures of Dengue Virus-Specific IL-10/IFN-γ Co-Producing CD4 T Cells and Their Association with Severe Dengue Disease (August 20, 2019). CELL-REPORTS-D-19-03008. Available at SSRN: https://ssrn.com/abstract=3439681 or http://dx.doi.org/10.2139/ssrn.3439681
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Yuan Tian (Contact Author)

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery

La Jolla, CA 92037
United States

Grégory Seumois

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery ( email )

La Jolla, CA 92037
United States

Luzia M. De-Oliveira-Pinto

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery ( email )

La Jolla, CA 92037
United States

Sara Herrera-de la Mata

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery ( email )

La Jolla, CA 92037
United States

Cheryl Kim

La Jolla Institute for Allergy and Immunology (LIAI) - Flow Cytometry Core Facility

La Jolla, CA 92037
United States

Denise Hinz

La Jolla Institute for Allergy and Immunology (LIAI) - Flow Cytometry Core Facility ( email )

La Jolla, CA 92037
United States

N.D. Suraj Goonawardhana

General Sir John Kotelawala Defense University - Department of Paraclinical Sciences ( email )

India

Aruna D. De Silva

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery ( email )

La Jolla, CA 92037
United States

Sunil Premawansa

University of Colombo - Department of Zoology and Environment Sciences ( email )

India

Gayani Premawansa

North Colombo Teaching Hospital ( email )

India

Ananda Wijewickrama

National Institute of Infectious Diseases ( email )

1-23-1 Toyama Shinjuku Yokyo
Japan

Angel Balmaseda

Ministry of Health, Nicaragua - National Laboratory of Virology ( email )

Nicaragua

Alba Grifoni

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery ( email )

La Jolla, CA 92037
United States

Pandurangan Vijayanand

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery

La Jolla, CA 92037
United States

Eva Harris

University of California, Berkeley - Division of Infectious Diseases and Vaccinology ( email )

United States

Bjoern Peters

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery

9420 Athena Cir
La Jolla, CA 92037
United States

Alessandro Sette

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery ( email )

La Jolla, CA 92037
United States

Daniela Weiskopf

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery ( email )

La Jolla, CA 92037
United States

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