Phenotype and functionality of follicular helper T cells in patients with acute dengue infection.
Wijesinghe A., Gamage J., Goonewardena H., Gomes L., Jayathilaka D., Wijeratne DT., de Alwis R., Jeewandara C., Wijewickrama A., Ogg GS., Malavige GN.
BackgroundThe association of functionality and phenotype of follicular helper T cells (Tfh) with dengue virus (DENV) specific antibody responses and clinical disease severity has not been well studied.MethodsWe investigated the phenotype and functionality of Tfh cells and plasmablasts in adult patients (DF = 18, DHF = 22) with acute dengue (day 4 to 8 since onset of fever) of varying severity using multiparametric flowcytometry. The properties of Tfh cells were correlated with viraemia, disease severity, plasmablast responses and DENV-specific serum antibody responses. We further evaluated the kinetics of neutralizing antibodies (Neut50) throughout the course of illness in order to evaluate their association with clinical disease severity and viraemia.ResultsTfh cells (especially those producing IL-21 and co-expressing PD-1 and ICOS) were found to be significantly expanded (p ConclusionsThe expansion of Tfh cells is associated with DHF and DENV-specific IgG, NS1-specific and neutralizing antibodies. Neut50 titres did not associate with disease severity or viraemia at the point of first presentation during the febrile phase, but later titres do show differential association with severity in patients with DENV1 compared to DENV2.