Characterization of Human CD8 T Cell Responses in Dengue Virus-Infected Patients from India

Abstract

Importance: Dengue is becoming a global public health concern. Although CD8 T-cells have been implicated in both protection and in cytokine-mediated immunopathology of dengue, how the balance maintained between these opposing functions remains unknown. We comprehensively characterized CD8 T-cell subsets in dengue-patients from India and Thailand; and show that these cells expand massively, express phenotypes indicative of overwhelming antigenic-stimulus, tissue homing/cytotoxic effector functions, but a vast majority of them fail to produce IFN-γ in vitro Interestingly, these cells were fully capable of producing the cytokine when stimulated in a TCR-independent manner, but failed to do so in a TCR dependent stimulation. These results, together with transcriptomics, revealed that a vast majority of these CD8 T-cells from dengue patients become cytokine unresponsive due to TCR-signalling insufficiencies. These observations open novel avenues for understanding the mechanisms that fine-tune the balance between CD8-mediated protective versus pathological effects during febrile dengue illness.