Tfh2 and a subset of Tfh1 cells associate with antibody-mediated immunity to malaria

Abstract

High-affinity antibody production depends on CD4+ T follicular helper (Tfh) cells. In humans, peripheral blood Tfh cells are heterogenous, as evidenced by differential expression of the chemokine receptors CXCR3 and CCR6, which to date have served to classify 3 subsets, pTfh1, pTfh2, and pTfh17. Although pTfh1 responses dominate during blood-stage Plasmodium infections, a clear association with protective antibody responses remains to be described. We hypothesized that pTfh cells exhibit greater phenotypic and functional heterogeneity than described by CXCR3/CCR6 and that more nuanced pTfh subsets play distinct roles during Plasmodium infection. We mapped pTfh cell heterogeneity in healthy i..