{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T08:07:09Z","timestamp":1793174829355,"version":"4.5.0"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T00:00:00Z","timestamp":1717977600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Follicular helper T cells are essential for helping in the maturation of B cells and the production of neutralizing antibodies (NAbs) during primary viral infections. However, their role during recall responses is unclear. Here, we used hepatitis C virus (HCV) reinfection in humans as a model to study the recall collaborative interaction between circulating CD4 T follicular helper cells (cTfh) and memory B cells (MBCs) leading to the generation of NAbs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We evaluated this interaction longitudinally in subjects who have spontaneously resolved primary HCV infection during a subsequent reinfection episode that resulted in either another spontaneous resolution (SR\/SR, <jats:italic>n<\/jats:italic> = 14) or chronic infection (SR\/CI, <jats:italic>n<\/jats:italic> = 8).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Both groups exhibited virus-specific memory T cells that expanded upon reinfection. However, early expansion of activated cTfh (CD4<jats:sup>+<\/jats:sup>CXCR5<jats:sup>+<\/jats:sup>PD-1<jats:sup>+<\/jats:sup>ICOS<jats:sup>+<\/jats:sup>FoxP3<jats:sup>\u2212<\/jats:sup>) occurred in SR\/SR only. The frequency of activated cTfh negatively correlated with time post-infection. Concomitantly, NAbs and HCV-specific MBCs (CD19<jats:sup>+<\/jats:sup>CD27<jats:sup>+<\/jats:sup>IgM<jats:sup>\u2212<\/jats:sup>E2-Tet<jats:sup>+<\/jats:sup>) peaked during the early acute phase in SR\/SR but not in SR\/CI. Finally, the frequency of the activated cTfh1 (CXCR3<jats:sup>+<\/jats:sup>CCR6<jats:sup>\u2212<\/jats:sup>) subset correlated with the neutralization breadth and potency of NAbs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results underscore a key role for early activation of cTfh1 cells in helping antigen-specific B cells to produce NAbs that mediate the clearance of HCV reinfection.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1403769","type":"journal-article","created":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T16:52:14Z","timestamp":1718124734000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Coordinated expansion of memory T follicular helper and B cells mediates spontaneous clearance of HCV 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