Early lymph node T follicular helper cell signalling hub drives influenza vaccine response in an ancestrally diverse cohort

作者：Jacqueline H. Y. Siu, Sofia Coelho, Aime Palomeras, Sandra Belij‐Rammerstorfer, Ninisha Barman, Chloe H. Lee, Tamara Ströbel, Christopher J. Thorpe, Charandeep Kaur, Tom Cole, Nico Remmert, Jamie Fowler, Sam Pledger, Kyla Dooley, Terrence Chan, Katja Höschler, Maria Zambon, Daniel Opoka, Tamás Szommer, Seung J. Kim, Vinod Kumar, Samantha Vanderslott, Pontiano Kaleebu, Anita Milicic, Donald B. Palmer, Teresa Lambe, Brian D. Marsden, Hashem Koohy, Mark Coles, Calliope A. Dendrou, Katrina M. Pollock · 发表于：EBioMedicine · 年份：2025 · DOI：10.1016/j.ebiom.2025.106036 · 被引用次数：1 · 研究领域：Influenza Virus Research Studies、T-cell and B-cell Immunology、interferon and immune responses

Background Early in vivo dynamics of human immune-cell activation across regionally activated lymphoid tissue sites upon immunisation are poorly characterised in ancestrally-diverse individuals with consequences for pandemic preparedness. Methods In this experimental medicine study, draining and non-draining lymph nodes (dLNs and ndLNs) were studied by ultrasound (US)-guided fine-needle aspiration (FNA) in 13 adults aged 18–55 years with African and Asian ancestry, before and after receiving adjuvanted seasonal influenza vaccine (aQIV). A multi-modal investigation of ultrasound data, genotyping, systems serology, and single-cell multi-omics was undertaken. Findings HLA subtypes reflected self-declared ethnicity and included understudied alleles. Draining but not ndLNs rapidly increased in size post-vaccination, by day 3, with distinct cellular dynamics culminating in a cross-protective serological response. Dissecting LN cellular diversity into 42 lymphoid and non-lymphoid cell states, early post-vaccination cell abundance changes were observed across all LNs, but dLNs were characterised by CD4 + T follicular helper (CD4 + Tfh) cell expansion. Gene expression analysis revealed a dLN post-vaccination hub defined by CD4 + Tfh signalling, cross-compartmental activation, translation, and enhanced antigen-presentation capacity. Interpretation Early CD4 + Tfh coordination in draining lymphoid tissue underpins robust responses to adjuvanted influenza vaccine that transcend ancestral...