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
Publication Status: Published
See all articles by Yuan Tian
La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery
La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery
La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery
La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery
La Jolla Institute for Allergy and Immunology (LIAI) - Flow Cytometry Core Facility
La Jolla Institute for Allergy and Immunology (LIAI) - Flow Cytometry Core Facility
General Sir John Kotelawala Defense University - Department of Paraclinical Sciences
La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery
University of Colombo - Department of Zoology and Environment Sciences
North Colombo Teaching Hospital
National Institute of Infectious Diseases
Ministry of Health, Nicaragua - National Laboratory of Virology
La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery
La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery
University of California, Berkeley - Division of Infectious Diseases and Vaccinology
La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery
La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery
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:
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). Available at SSRN: https://ssrn.com/abstract=3439681 or http://dx.doi.org/10.2139/ssrn.3439681
This version of the paper has not been formally peer reviewed.
La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery
La Jolla, CA 92037
United States
La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery ( email )
La Jolla, CA 92037
United States
La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery ( email )
La Jolla, CA 92037
United States
La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery ( email )
La Jolla, CA 92037
United States
La Jolla Institute for Allergy and Immunology (LIAI) - Flow Cytometry Core Facility
La Jolla, CA 92037
United States
La Jolla Institute for Allergy and Immunology (LIAI) - Flow Cytometry Core Facility ( email )
La Jolla, CA 92037
United States
General Sir John Kotelawala Defense University - Department of Paraclinical Sciences ( email )
India
La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery ( email )
La Jolla, CA 92037
United States
University of Colombo - Department of Zoology and Environment Sciences ( email )
India
North Colombo Teaching Hospital ( email )
India
National Institute of Infectious Diseases ( email )
1-23-1 Toyama Shinjuku Yokyo
Japan
Ministry of Health, Nicaragua - National Laboratory of Virology ( email )
Nicaragua
La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery ( email )
La Jolla, CA 92037
United States
La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery
La Jolla, CA 92037
United States
University of California, Berkeley - Division of Infectious Diseases and Vaccinology ( email )
United States
La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery
9420 Athena Cir
La Jolla, CA 92037
United States
La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery ( email )
La Jolla, CA 92037
United States
La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery ( email )
La Jolla, CA 92037
United States
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