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Expression data from the CD8 T cells of healthy donors and dengue patients from Thailand

ABSTRACT: CD8 T cells play roles in eliminating virus infected targets through cytotoxic effector function and are of great interest from vaccination prespective. Previous studies suggest that the cytokines produced by the CD8 T cells may contribute to the pathological consequences. Because the dengue specific memory T cells strongly secrete cytokines upon in vitro stimulation with heterologous viral antigen, the ‘cytokine storm’ induced by activated T cells may contribute to the immunopathology of dengue infection. Moreover, the CD8 T cell expansion peaks before or around the time of the peak of clinical symptoms, and the frequency of activated CD8 T cells and cytokine producing cells was somewhat higher in patients with severe forms of dengue disease. To gain further insight into the characteristics of activated CD8 T cells, we performed microarray analysis of the HLA-DR+CD38+ CD8 T cells that were sorted from the PBMCs of seven dengue patients from Siriraj Hospital in Bangkok, Thailand and compare with the sorted naive (CCR7+CD45RA+) CD8 T cells from five Thai healthy donors.

ORGANISM(S): Homo sapiens

PROVIDER: GSE84331 | GEO | 2016/10/05

SECONDARY ACCESSION(S): PRJNA328920

REPOSITORIES: GEO

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Project description:Dengue virus (DENV) infects hundreds of millions of people annually, yet there is only a limited knowledge of the host immune response to dengue. Here, we used a systems biological approach to perform a detailed analysis of the innate immune response to DENV infection in the whole blood samples of acutely infected humans in Bangkok, Thailand. Transcriptomic analysis revealed that genes encoding pro-inflammatory mediators and type I IFN related proteins, were associated with high levels of virus during the first few days of infection. Individuals with low or negative viremia at the late stage of fever were enriched with genes associated with pathways involved in cell cycle, proliferation, cell metabolism and translational control. Meta-analysis showed significant enrichment in genes specific for innate cells (monocytes, macrophages and DCs) in the specimens with high VL and enrichment in genes specific for NK cells, CD4+ and CD8+ T cells as well as B cells in specimens with low VL. Furthermore, flow cytometric analysis revealed an expansion in the numbers of CD14+CD16+ monocytes and depletion of CD14dimCD16++ cells and BDCA-1+ myeloid DC in blood. Consistent with this, in a non-human primate model, infection with DENV boosted the numbers of CD14+CD16+ monocytes in the blood and in secondary lymphoid organs. In vitro, freshly isolated blood monocytes infected with DENV up regulated CD16 and mediated robust differentiation of resting B cells to CD27++CD38++ plasmablasts and IgG and IgM secretion. Taken together, these data provide a detailed picture of the innate response to dengue infection in humans, and highlight an unappreciated role for CD14+CD16+ monocytes in promoting the differentiation of plasmablasts and mediating antibody response to DENV. We analyzed whole blood samples from 28 dengue patients (DF n=18, DHF=10) hospitalized at the Siriraj Hospital in Bangkok, Thailand during the season of 2009 The specimens were acquired between days 2 and 9 after onset of symptoms (acute illness), and for 19 patients (DF n=13, DHF=6) also at the convalescence at 4 weeks or later after discharge. Additionally, blood was sampled from 9 healthy, non-infected donors to provide controls for transcriptomic and immunological analysis.

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Expression data from the CD8 T cells of healthy donors and dengue patients from Thailand

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