PD-1highCXCR5–CD4+ Peripheral Helper T (Tph) cells Promote CXCR3+ Plasmablasts in the early phase of COVID-19

T cell–B cell interaction is the key immune response to protect host from severe viral infection. We used COVID-19 as a model of acute viral infections and analyzed CD4+ T cell subsets associated with plasmablasts expansion and clinical outcome. Peripheral helper T cells (Tph, denoted as PD-1highCXCR5–CD4+ T cells) were significantly increased, as were plasmablasts. Tph cells exhibited “B-cell help” signatures and induced plasmablasts differentiation in vitro. Expanded plasmablasts showed increased CXCR3 expression, which is positively correlated with higher frequency of activated Tph cells and better clinical outcome. These results elucidate a critical role for Tph cells in regulating protective B cell response during acute viral infection. Overall design: sorted 6 subsets of CD4+CD45RA- T cells based on PD-1 and CXCR5 expressions from 3 patients with COVID-19