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

tetano

Editor, Senior Moderator
Nat Immunol


. 2024 Aug 20.
doi: 10.1038/s41590-024-01926-6. Online ahead of print. Influenza vaccination stimulates maturation of the human T follicular helper cell response

Stefan A Schattgen[SUP] #[/SUP][SUP] 1 [/SUP], Jackson S Turner[SUP] #[/SUP][SUP] 2 [/SUP], Mohamed A Ghonim[SUP] #[/SUP][SUP] 1 [/SUP], Jeremy Chase Crawford[SUP] 1 [/SUP], Aaron J Schmitz[SUP] 2 [/SUP], Hyunjin Kim[SUP] 1 [/SUP], Julian Q Zhou[SUP] 2 [/SUP], Walid Awad[SUP] 1 [/SUP], Robert C Mettelman[SUP] 1 [/SUP], Wooseob Kim[SUP] 2 3 [/SUP], Katherine M McIntire[SUP] 2 [/SUP], Alem Haile[SUP] 4 [/SUP], Michael K Klebert[SUP] 4 [/SUP], Teresa Suessen[SUP] 5 [/SUP], William D Middleton[SUP] 5 [/SUP], Sharlene A Teefey[SUP] 5 [/SUP], Rachel M Presti[SUP] 6 [/SUP], Ali H Ellebedy[SUP] 7 8 9 [/SUP], Paul G Thomas[SUP] 10 [/SUP]



Affiliations
Abstract

The differentiation and specificity of human CD4[SUP]+[/SUP] T follicular helper cells (T[SUB]FH[/SUB] 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[SUP]+[/SUP] T[SUB]FH[/SUB] cell response. The first vaccination induced an increase in the frequency of circulating T[SUB]FH[/SUB] (cT[SUB]FH[/SUB]) and LN T[SUB]FH[/SUB] cells at week 1 postvaccination. This increase was transient for cT[SUB]FH[/SUB] cells, whereas the LN T[SUB]FH[/SUB] cells further expanded during week 2 and remained elevated in frequency for at least 3 months. We observed several distinct subsets of T[SUB]FH[/SUB] cells in the LN, including pre-T[SUB]FH[/SUB] cells, memory T[SUB]FH[/SUB] cells, germinal center (GC) T[SUB]FH[/SUB] cells and interleukin-10[SUP]+[/SUP] T[SUB]FH[/SUB] cell subsets beginning at baseline and at all time points postvaccination. The shift toward a GC T[SUB]FH[/SUB] cell phenotype occurred with faster kinetics after the second vaccine compared to the first vaccine. We identified several influenza-specific T[SUB]FH[/SUB] cell clonal lineages, including multiple responses targeting internal influenza virus proteins, and found that each T[SUB]FH[/SUB] cell state was attainable within a clonal lineage. Thus, human T[SUB]FH[/SUB] cells form a durable and dynamic multitissue network.


 
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