TY - JOUR
T1 - Influenza vaccination stimulates maturation of the human T follicular helper cell response
AU - Schattgen, Stefan A.
AU - Turner, Jackson S.
AU - Ghonim, Mohamed A.
AU - Crawford, Jeremy Chase
AU - Schmitz, Aaron J.
AU - Kim, Hyunjin
AU - Zhou, Julian Q.
AU - Awad, Walid
AU - Mettelman, Robert C.
AU - Kim, Wooseob
AU - McIntire, Katherine M.
AU - Haile, Alem
AU - Klebert, Michael K.
AU - Suessen, Teresa
AU - Middleton, William D.
AU - Teefey, Sharlene A.
AU - Presti, Rachel M.
AU - Ellebedy, Ali H.
AU - Thomas, Paul G.
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/9
Y1 - 2024/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85201965032&partnerID=8YFLogxK
U2 - 10.1038/s41590-024-01926-6
DO - 10.1038/s41590-024-01926-6
M3 - Article
C2 - 39164477
AN - SCOPUS:85201965032
SN - 1529-2908
VL - 25
SP - 1742
EP - 1753
JO - Nature immunology
JF - Nature immunology
IS - 9
ER -