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

  • Nicholas Borcherding,
  • Wooseob Kim,
  • Michael Quinn,
  • Fangjie Han,
  • Julian Q. Zhou,
  • Alexandria J. Sturtz,
  • Aaron J. Schmitz,
  • Tingting Lei,
  • Stefan A. Schattgen,
  • Michael K. Klebert,
  • Teresa Suessen,
  • William D. Middleton,
  • Charles W. Goss,
  • Chang Liu,
  • Jeremy Chase Crawford,
  • Paul G. Thomas,
  • Sharlene A. Teefey,
  • Rachel M. Presti,
  • Jane A. O’Halloran,
  • Jackson S. Turner,
  • Ali H. Ellebedy,
  • Philip A. Mudd

摘要

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.