Influenza vaccination stimulates maturation of the human T follicular helper cell response

Stefan A. Schattgen, Jackson S. Turner, Mohamed A. Ghonim, Jeremy Chase Crawford, Aaron J. Schmitz, Hyunjin Kim, Julian Q. Zhou, Walid Awad, Robert C. Mettelman, Wooseob Kim, Katherine M. McIntire, Alem Haile, Michael K. Klebert, Teresa Suessen, William D. Middleton, Sharlene A. Teefey, Rachel M. Presti, Ali H. Ellebedy, Paul G. Thomas

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

The differentiation and specificity of human CD4+ T follicular helper cells (TFH cells) after influenza vaccination have been poorly defined. Here we profiled blood and draining lymph node (LN) samples from human volunteers for over 2 years after two influenza vaccines were administered 1 year apart to define the evolution of the CD4+ TFH cell response. The first vaccination induced an increase in the frequency of circulating TFH (cTFH) and LN TFH cells at week 1 postvaccination. This increase was transient for cTFH cells, whereas the LN TFH cells further expanded during week 2 and remained elevated in frequency for at least 3 months. We observed several distinct subsets of TFH cells in the LN, including pre-TFH cells, memory TFH cells, germinal center (GC) TFH cells and interleukin-10+ TFH cell subsets beginning at baseline and at all time points postvaccination. The shift toward a GC TFH cell phenotype occurred with faster kinetics after the second vaccine compared to the first vaccine. We identified several influenza-specific TFH cell clonal lineages, including multiple responses targeting internal influenza virus proteins, and found that each TFH cell state was attainable within a clonal lineage. Thus, human TFH cells form a durable and dynamic multitissue network.

Original languageEnglish
Pages (from-to)1742-1753
Number of pages12
JournalNature immunology
Volume25
Issue number9
DOIs
StatePublished - Sep 2024

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