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Nat Immunol . CD4+ T cells exhibit distinct transcriptional phenotypes in the lymph nodes and blood following mRNA vaccination in humans

tetano

Editor, Senior Moderator
Nat Immunol


. 2024 Aug 20.
doi: 10.1038/s41590-024-01888-9. Online ahead of print. CD4[SUP]+[/SUP] T cells exhibit distinct transcriptional phenotypes in the lymph nodes and blood following mRNA vaccination in humans

Nicholas Borcherding[SUP] 1 [/SUP], Wooseob Kim[SUP] 1 2 [/SUP], Michael Quinn[SUP] 3 [/SUP], Fangjie Han[SUP] 4 [/SUP], Julian Q Zhou[SUP] 1 [/SUP], Alexandria J Sturtz[SUP] 1 [/SUP], Aaron J Schmitz[SUP] 1 [/SUP], Tingting Lei[SUP] 1 [/SUP], Stefan A Schattgen[SUP] 5 [/SUP], Michael K Klebert[SUP] 6 [/SUP], Teresa Suessen[SUP] 7 [/SUP], William D Middleton[SUP] 7 [/SUP], Charles W Goss[SUP] 8 [/SUP], Chang Liu[SUP] 1 [/SUP], Jeremy Chase Crawford[SUP] 5 [/SUP], Paul G Thomas[SUP] 5 [/SUP], Sharlene A Teefey[SUP] 7 [/SUP], Rachel M Presti[SUP] 6 9 10 11 [/SUP], Jane A O'Halloran[SUP] 9 [/SUP], Jackson S Turner[SUP] 1 [/SUP], Ali H Ellebedy[SUP] 12 13 14 [/SUP], Philip A Mudd[SUP] 15 16 17 [/SUP]



Affiliations
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and mRNA vaccination induce robust CD4[SUP]+[/SUP] T cell responses. Using single-cell transcriptomics, here, we evaluated CD4[SUP]+[/SUP] T cells specific for the SARS-CoV-2 spike protein in the blood and draining lymph nodes (dLNs) of individuals 3 months and 6 months after vaccination with the BNT162b2 mRNA vaccine. We analyzed 1,277 spike-specific CD4[SUP]+[/SUP] T cells, including 238 defined using Trex, a deep learning-based reverse epitope mapping method to predict antigen specificity. Human dLN spike-specific CD4[SUP]+[/SUP] follicular helper T (T[SUB]FH[/SUB]) cells exhibited heterogeneous phenotypes, including germinal center CD4[SUP]+[/SUP] T[SUB]FH[/SUB] cells and CD4[SUP]+[/SUP]IL-10[SUP]+[/SUP] T[SUB]FH[/SUB] cells. Analysis of an independent cohort of SARS-CoV-2-infected individuals 3 months and 6 months after infection found spike-specific CD4[SUP]+[/SUP] T cell profiles in blood that were distinct from those detected in blood 3 months and 6 months after BNT162b2 vaccination. Our findings provide an atlas of human spike-specific CD4[SUP]+[/SUP] T cell transcriptional phenotypes in the dLNs and blood following SARS-CoV-2 vaccination or infection.


 
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