{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T04:38:37Z","timestamp":1763008717338,"version":"3.45.0"},"reference-count":168,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":295,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012187","name":"St. Vincent's Clinic Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012187","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin &amp; Trans Imm"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      CD4\n                      <jats:sup>+<\/jats:sup>\n                      T\u00a0cells partitioned into different cell lineages based on transcription factor, cytokine and chemokine expression have defined functions that work cooperatively to ensure optimum operation of the immune system. This study investigated the lineages and interactions of key CD4\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cell subsets within human lymph nodes (LNs) post\u2010vaccination to assess the potential for adaptability and flexibility in an immune response.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Ultrasound\u2010guided fine needle biopsies\/aspirates were used to isolate T follicular helper (Tfh) and Precursor (Pre)\u2010Tfh cells from the vaccine\u2010draining and contralateral axillary LNs of five individuals at 5\u2009days after influenza vaccination, followed by single\u2010cell RNA sequencing, gene expression and T\u2010cell receptor analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Tfh and Pre\u2010Tfh cells within five clusters with distinct gene expression profiles, designated: Resting, Activated migrating, B\u2010cell\u2010interacting Tfh, Proliferating and Cytotoxic, exhibited attributes of more than one T\u2010cell lineage and expanded T\u2010cell clones were present in more than one cluster, suggesting divergent differentiation into different fate lineages from a common precursor. Inferred pseudotime suggested a bifurcating trajectory rooted in the resting cluster and terminating at either the Proliferating or Cytotoxic clusters. This analysis predicted the transition of cells through activation states and the gain and loss of lineage attributes and effector functions. Enriched gene pathways along the pseudotime trajectories were consistent with these functional transitions and involvement in the immune response to vaccination.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These results reveal the flexible potential within the Tfh lineage that could be leveraged to drive more efficient vaccine responses and inform rational vaccine design.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cti2.70056","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T06:52:13Z","timestamp":1761288733000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Human axillary lymph node T follicular helper (Tfh) and Precursor\u2010Tfh cells exhibit functional flexibility following seasonal influenza vaccination"],"prefix":"10.1002","volume":"14","author":[{"given":"Hannah","family":"Law","sequence":"first","affiliation":[{"name":"Immunovirology and Pathogenesis Program, Kirby Institute UNSW Sydney  Sydney NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9384-2447","authenticated-orcid":false,"given":"Raymond H. 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