Transcriptomic analysis of DENV-specific CD8+T cell responses in acute disease does not support qualitative differences as drivers of disease severity

In this study, we assessed the contribution of dengue-specific CD8+T cells in hospitalized samples with mild (dengue fever; DF) and severe (dengue hemorrhagic fever; DHF) forms of the disease. Our in-depth transcriptomic analysis provides no evidence for qualitative differences in terms of CD8+T cell response against dengue, therefore, concluding that CD8+T cell response is not a contributing factor in the development of severe dengue disease. 40 individuals that required hospitalization due to DENV infection (based on clinical diagnosis and being positive either with PCR or IgM serology assay), have been enrolled and the corresponding blood samples were collected during hospitalization and during a follow up visit in convalescent phase. The 40 individuals are classified based on diseases severity in 20 with the mild form of the disease (Dengue Fever; DF) and 20 with the most severe form of the disease (Dengue Hemorragic Fever; DHF). For each donor, PBMCs purified from the blood samples have been stimulated with DENV-specific pool of class I peptides for 6 hours followed by IFNg capture assay. After stimulation, the CD8+CD3+ cells have been sorted based on being IFNg positive or IFNg negative and both conditions were sequenced using a microscaled approach.