Dataset Information

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

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-?+ 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.

SUBMITTER: Tian Y

PROVIDER: S-EPMC6942518 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Publications

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

Tian Yuan Y Seumois Grégory G De-Oliveira-Pinto Luzia M LM Mateus Jose J Herrera-de la Mata Sara S Kim Cheryl C Hinz Denise D Goonawardhana N D Suraj NDS de Silva Aruna D AD Premawansa Sunil S Premawansa Gayani G Wijewickrama Ananda A Balmaseda Angel A Grifoni Alba A Vijayanand Pandurangan P Harris Eva E Peters Bjoern B Sette Alessandro A Weiskopf Daniela D

Cell reports 20191201 13

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<sup>+</sup>IFN-γ<sup>+</sup> 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 r ...[more]

PMID: 31875555

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Project description:Dengue virus (DENV) infection is associated with a range of clinical manifestations, from self-limiting dengue fever (DF) to life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Although DENV-specific CD4 T cells are capable of producing inflammatory cytokines and can acquire cytotoxic functions in previously DENV-exposed individuals, much less is known related to DENV-specific CD4 T cells during acute DENV infection and disease. In this study, we set out to characterize the immune signatures of DENV-specific CD4 T cells during acute infection and investigate whether DENV-specific CD4 T cell response differs between DF and DHF. Previous studies suggest that increased IL-10 level in the blood is associated with severe dengue disease. Here we show evidence of DENV-specific IL-10-producing CD4 T cells during acute DENV infection. More specifically, an IL-10+IFN-γ+ double positive (DP) CD4 T cell population was prominent in acute hospitalized DENV cases but disappeared at the convalescent stage. RNA-sequencing analysis revealed that these cells were associated with gene signatures that marginally overlapped with previously identified signatures of cytotoxic CD4 T cells and type 1 regulatory T (Tr1)-like cells. However, the majority of the genes differentially expressed by DP cells were not related to cytotoxic CD4 T cells or Tr1-like cells. These genes include IL-21, IL-22, CD86, CD109, and CCR1, which are involved in T cell activation, function, cytokine signaling, and migration. Notably, the magnitude of DP cell response was higher in DHF than DF, whereas the gene expression profile of DP cells was similar between DF and DHF. Finally, our data show that DENV-specific DP cells are largely homogeneous based on the expression of 31 selected markers. Overall, this study reveals unique phenotypes of virus-specific IL-10/IFN-γ co-producing CD4 cells and indicates that the quantity but not quality of these cells may be positively correlated with dengue disease severity.

Dataset Information

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

Publications

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

Similar Datasets

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