Activation of Peripheral T Follicular Helper Cells During Acute Dengue Virus Infection

Background. Follicular helper T cells (T-FH) are specialized CD4 T cells required for B-cell help and antibody production. Methods. Given the postulated role of immune activation in dengue disease, we measured the expansion and activation of T-FH in the circulation (peripheral T-FH [pT(FH)]) collected from Thai children with laboratory-confirmed acute dengue virus (DENV) infection. Results. We found significant expansion and activation of pT(FH) subsets during acute infection with the highest frequencies of activated pT(FH) (PD1(hi) pT(FH) and PD1(+) CD38(+) pT(FH)) detected during the critical phase of illness. Numbers of activated pT(FH) were higher in patients with secondary compared with primary infections and in patients with more severe disease. We also found a positive correlation between the frequencies of activated pT(FH) and the frequencies of plasmablasts. Conclusions. To our knowledge, this is the first ex vivo analysis of pT(FH) activation during acute DENV infection. Overall, our study supports the model that pT(FH) contribute to disease evolution during the critical stage of illness.