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

• Published in: Cell reports (Cambridge) Vol. 29; no. 13; pp. 4482 - 4495.e4
• Main Authors: 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, Weiskopf, Daniela
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 24.12.2019; Elsevier
• Subjects: acute dengue; Adolescent; Adult; Antigens, CD - genetics; Antigens, CD - immunology; Case-Control Studies; CD4 T cell; CyTOF; dengue fever; dengue hemorrhagic fever; dengue virus; Dengue Virus - immunology; Dengue Virus - pathogenicity; Female; Gene Expression Regulation - immunology; GPI-Linked Proteins - genetics; GPI-Linked Proteins - immunology; Humans; IFN-γ; IL-10; Interferon-gamma - genetics; Interferon-gamma - immunology; Interleukin-10 - genetics; Interleukin-10 - immunology; Interleukin-22; Interleukins - genetics; Interleukins - immunology; Male; Middle Aged; Neoplasm Proteins - genetics; Neoplasm Proteins - immunology; Receptors, CCR1 - genetics; Receptors, CCR1 - immunology; RNA-seq; Severe Dengue - genetics; Severe Dengue - immunology; Severe Dengue - pathology; Severe Dengue - virology; Severity of Illness Index; Signal Transduction; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - virology; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - virology; Transcriptome - immunology; transcriptomics; dengue hemorrhagic fever; IFN-γ; dengue fever; RNA-seq; CD4 T cell; dengue virus; transcriptomics; CyTOF; IL-10; acute dengue
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2019.11.098

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. [Display omitted] •DENV-specific IL-10+IFN-γ+ DP CD4 T cells are prominent during acute disease•Most DP cell DE genes are non-cytotoxic/Tr1 and include IL21, IL22, CD109, and CCR1•DP cells have similar gene expression in DF and DHF, despite higher frequency in DHF•Disease severity is not associated with altered DP cell phenotype or functionality 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.