{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T15:30:36Z","timestamp":1785339036184,"version":"3.55.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,8,30]],"date-time":"2025-08-30T00:00:00Z","timestamp":1756512000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"AMED-CREST","award":["19gm1310002"],"award-info":[{"award-number":["19gm1310002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Vaccines effectively stimulate protective immune responses in healthy individuals, but the precise roles of germinal center (GC) and follicular helper T (TFH) cells in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine responses are not fully understood. This study used a conditional loss-of-function mouse model to investigate antibody responses to the Wuhan spike protein, specifically eliminating newly developed TFH cells during either the primary or memory phase. Our findings demonstrated that TFH-mediated GC responses are essential for primary vaccination. However, after booster immunization, memory B-cell responses were effectively regulated through extrafollicular mechanisms, independent of TFH cells. Ablating IL-4 receptor signaling in B cells attenuated antibody production in both the primary and memory phases, highlighting the critical role of IL-4 for optimal humoral immunity. We identified a unique population of IL-4-expressing memory T (IL-4+Tm) cells, characterized by CD27, GATA3, and IRF4 expression, that is strongly associated with these extrafollicular memory B-cell responses, capable of neutralizing SARS-CoV-2 variants. Furthermore, Omicron-based booster immunization recovered the immunity against emerging variants under TFH-deficient conditions. These results suggest that IL-4+Tm cells are an alternative pathway to sustain memory responses when GC function is impaired, particularly in immunocompromised states. Our study advances the understanding of memory T-cell-mediated humoral responses to SARS-CoV-2, offering insights for future vaccine strategies.<\/jats:p>","DOI":"10.1093\/intimm\/dxaf051","type":"journal-article","created":{"date-parts":[[2025,8,30]],"date-time":"2025-08-30T09:05:21Z","timestamp":1756544721000},"page":"41-55","source":"Crossref","is-referenced-by-count":1,"title":["The role of IL-4+ memory T cells in SARS-CoV-2 booster vaccination"],"prefix":"10.1093","volume":"38","author":[{"given":"Jumana","family":"Khalil","sequence":"first","affiliation":[{"name":"Division of Molecular Pathology, Research Institute for Biomedical Science, Tokyo University of Science , Chiba ,\u00a0","place":["Japan"]},{"name":"Department of Immunology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku , Kyoto 606-8501 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