ResearchIn-Press PreviewImmunologyVaccines
Open Access | 10.1172/jci.insight.180667
1Division of Rheumatology, University of Pennsylvania, Philadelphia, United States of America
2Department of Microbiology and Immunology, Emory University, Atlanta, United States of America
Find articles by Pan, Y. in: JCI | PubMed | Google Scholar
1Division of Rheumatology, University of Pennsylvania, Philadelphia, United States of America
2Department of Microbiology and Immunology, Emory University, Atlanta, United States of America
Find articles by Bartolo, L. in: JCI | PubMed | Google Scholar
1Division of Rheumatology, University of Pennsylvania, Philadelphia, United States of America
2Department of Microbiology and Immunology, Emory University, Atlanta, United States of America
Find articles by Xu, R. in: JCI | PubMed | Google Scholar
1Division of Rheumatology, University of Pennsylvania, Philadelphia, United States of America
2Department of Microbiology and Immunology, Emory University, Atlanta, United States of America
Find articles by Patel, B. in: JCI | PubMed | Google Scholar
1Division of Rheumatology, University of Pennsylvania, Philadelphia, United States of America
2Department of Microbiology and Immunology, Emory University, Atlanta, United States of America
Find articles by Zarnitsyna, V. in: JCI | PubMed | Google Scholar
1Division of Rheumatology, University of Pennsylvania, Philadelphia, United States of America
2Department of Microbiology and Immunology, Emory University, Atlanta, United States of America
Find articles by Su, L. in: JCI | PubMed | Google Scholar
Published June 11, 2024 - More info
Memory T cells are conventionally associated with durable recall responses. In our longitudinal analyses of CD4+ T cell responses to the yellow fever virus (YFV) vaccine by peptide-MHC tetramers, we unexpectedly found CD45RO-CCR7+ virus-specific CD4+ T cells that expanded shortly after vaccination and persisted months to years after immunization. Further phenotypic analyses revealed the presence of stem-cell memory T cells (TSCM) within this subset. In addition, post-vaccine T cells lacking known memory markers and functionally resembling genuine naïve T cells were identified, referred to herein as marker-negative T cells (TMN). Single-cell TCR sequencing detected expanded clonotypes within the TMN subset and identified TMN TCRs shared with memory and effector T cells. Longitudinal tracking of YFV-specific responses over subsequent years revealed superior stability of TMN cells, which correlated with the longevity of the overall tetramer+ population. These findings uncovered additional complexity within the post-immune T cell compartment and implicate TMN cells in durable immune responses.