T-cell responses to dengue virus in humans

Abstract

Dengue virus (DENV) is a leading cause of morbidity and mortality in most tropical and subtropical areas of the world. Dengue virus infection induces specific CD4+CD8- and CD8+CD4- T cells in humans. In primary infection, T-cell responses to DENV are serotype cross-reactive, but the highest response is to the serotype that caused the infection. The epitopes recognized by DENV-specific T cells are located in most of the structural and non-structural proteins, but NS3 is the protein that is most dominantly recognized. In patients with dengue hemorrhagic fever (DHF) caused by secondary DENV infection, T cells are highly activated in vivo. These highly activated T cells are DENV-specific and oligoclonal. Multiple kinds of lymphokines are produced by the activated T cells, and it has been hypothesized that these lymphokines are responsible for induction of plasma leakage, one of the most characteristic features of DHF. Thus, T-cells play important roles in the pathogenesis of DHF and in the recovery from DENV infection.

Keywords: Dengue fever; Dengue hemorrhagic fever; Dengue virus; T-cell receptor; T-cell response.

Fig. 1.

T-cell receptor usage in PBMCs collected from a patient with DHF. TCR VB usage in PBMC from a patient with DHF. PBMCs were collected on days –4, –2, 2 and 180, where day 0 is defined as the day of defervescence.

Fig. 2.

Delta scores of TCR AV and BV. Delta scores were compared between acute and convalescent stages. P < 0.01 between acute and convalescent stages in TCR AV and BV.

Fig. 3.

Relationship between TCR delta scores and the severity of dengue illness. There was a positive relationship between delta scores and severity of dengue illness in TCR BV usage.

Fig. 4.

Size spectratyping of CDR3 of selected TCRs in PBMCs obtained from patients with DF and DHF. PBMCs were collected on days –4, –2, 2 and 180, where day 0 is defined as the day of defervescence.