TY - JOUR
T1 - CD4+ T cells exhibit distinct transcriptional phenotypes in the lymph nodes and blood following mRNA vaccination in humans
AU - Borcherding, Nicholas
AU - Kim, Wooseob
AU - Quinn, Michael
AU - Han, Fangjie
AU - Zhou, Julian Q.
AU - Sturtz, Alexandria J.
AU - Schmitz, Aaron J.
AU - Lei, Tingting
AU - Schattgen, Stefan A.
AU - Klebert, Michael K.
AU - Suessen, Teresa
AU - Middleton, William D.
AU - Goss, Charles W.
AU - Liu, Chang
AU - Crawford, Jeremy Chase
AU - Thomas, Paul G.
AU - Teefey, Sharlene A.
AU - Presti, Rachel M.
AU - O’Halloran, Jane A.
AU - Turner, Jackson S.
AU - Ellebedy, Ali H.
AU - Mudd, Philip A.
N1 - Publisher Copyright:
© Springer Nature America, Inc. 2024.
PY - 2024/9
Y1 - 2024/9
N2 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and mRNA vaccination induce robust CD4+ T cell responses. Using single-cell transcriptomics, here, we evaluated CD4+ 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+ T cells, including 238 defined using Trex, a deep learning-based reverse epitope mapping method to predict antigen specificity. Human dLN spike-specific CD4+ follicular helper T (TFH) cells exhibited heterogeneous phenotypes, including germinal center CD4+ TFH cells and CD4+IL-10+ TFH cells. Analysis of an independent cohort of SARS-CoV-2-infected individuals 3 months and 6 months after infection found spike-specific CD4+ 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+ T cell transcriptional phenotypes in the dLNs and blood following SARS-CoV-2 vaccination or infection.
AB - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and mRNA vaccination induce robust CD4+ T cell responses. Using single-cell transcriptomics, here, we evaluated CD4+ 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+ T cells, including 238 defined using Trex, a deep learning-based reverse epitope mapping method to predict antigen specificity. Human dLN spike-specific CD4+ follicular helper T (TFH) cells exhibited heterogeneous phenotypes, including germinal center CD4+ TFH cells and CD4+IL-10+ TFH cells. Analysis of an independent cohort of SARS-CoV-2-infected individuals 3 months and 6 months after infection found spike-specific CD4+ 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+ T cell transcriptional phenotypes in the dLNs and blood following SARS-CoV-2 vaccination or infection.
UR - http://www.scopus.com/inward/record.url?scp=85201969279&partnerID=8YFLogxK
U2 - 10.1038/s41590-024-01888-9
DO - 10.1038/s41590-024-01888-9
M3 - Article
C2 - 39164479
AN - SCOPUS:85201969279
SN - 1529-2908
VL - 25
SP - 1731
EP - 1741
JO - Nature immunology
JF - Nature immunology
IS - 9
ER -