biostudies-literatureAsashima HNCATS NIH HHSNIA NIH HHSNIAID NIH HHSNHLBI NIH HHSNINDS NIH HHSNCI NIH HHS111895https://www.ebi.ac.uk/biostudies/studies/S-EPMC9806868biostudies-literatureUnknown42(1)T cell-B cell interaction is the key immune response to protect the host from severe viral infection. However, how T cells support B cells to exert protective humoral immunity in humans is not well understood. Here, we use COVID-19 as a model of acute viral infections and analyze CD4⁺ T cell subsets associated with plasmablast expansion and clinical outcome. Peripheral helper T cells (Tph cells; denoted as PD-1^highCXCR5^-CD4⁺ T cells) are significantly increased, as are plasmablasts. Tph cells exhibit "B cell help" signatures and induce plasmablast differentiation in vitro. Interestingly, expanded plasmablasts show increased CXCR3 expression, which is positively correlated with higher frequency of activated Tph cells and better clinical outcome. MCell reportsPD-1^highCXCR5^-CD4⁺ peripheral helper T cells promote CXCR3⁺ plasmablasts in human acute viral infection.PMC9806868U01 HL145567UL1 TR001863R01 AI157488R01 AI104739R01 CA227473P50 CA121974K24 AG042489R25 NS079193P01 AI039671R01 HL127349P01 AI073748U19 AI089992R01 HL141852R01 NS111242Mohanty SChaudhary OWong PHafler DARaddassi KKlein JUnterman ALucas CCoffey SEmu BLele NIwasaki AMontgomery RRAsashima HComi MKleinstein SHRuff WECohen IGreta LShaw ACHoehn KBDela Cruz CSKaminski NSumida TSfalsePD-1^highCXCR5^-CD4⁺ peripheral helper T cells promote CXCR3⁺ plasmablasts in human acute viral infection.T cell-B cell interaction is the key immune response to protect the host from severe viral infection. However, how T cells support B cells to exert protective humoral immunity in humans is not well understood. Here, we use COVID-19 as a model of acute viral infections and analyze CD4⁺ T cell subsets associated with plasmablast expansion and clinical outcome. Peripheral helper T cells (Tph cells; denoted as PD-1^highCXCR5^-CD4⁺ T cells) are significantly increased, as are plasmablasts. Tph cells exhibit "B cell help" signatures and induce plasmablast differentiation in vitro. Interestingly, expanded plasmablasts show increased CXCR3 expression, which is positively correlated with higher frequency of activated Tph cells and better clinical outcome. M2023-01-01T00:00:00Z2023 Jan2025-04-19T13:28:43.643Z2025-02-18T23:35:44.605ZS-EPMC98068683659630310.1016/j.celrep.2022.111895