Immunity & infection
Antibodies play crucial role in dengue virus pathogenesis and disease severity. Understanding the factors decisive of optimal antibody responses is essential for the rational development of dengue vaccine. In this study, we sought to determine the traits and function of CD4 T helper cell subsets in formulating antibody response to dengue virus. Here, in longitudinal and antigen-specific analyses we demonstrate the existence of a novel T helper (Th)-subset that displays follicular T helper (Tfh)-like characteristics and expands robustly in the critical phase of dengue, together with conventional Tfh cells. Moreover, the novel Th subset harbors the potential of B-cell help in terms of expressing key help factors; IL21, CD40L, IL10 and IFNγ. We further demonstrate that IgG responses to NS1 are independent of germinal center (GC) reaction and that novel Th subset is superior to Tfh subset in inducing plasma cell differentiation and NS1 specific IgG in autologous T-B co-cultures. Our work describes the existence of a unique CD4 T helper subset as an underlying determinant of excessive antibody responses in dengue, which has implication for the rational development of vaccine and therapy.