%0 Journal Article
%T Preservation of naive-phenotype CD4+ T cells after vaccination contributes to durable immunity.
%A Pan YG
%A Bartolo L
%A Xu R
%A Patel BV
%A Zarnitsyna VI
%A Su LF
%J JCI Insight
%V 9
%N 14
%D 2024 Jun 11
%M 38861490
%F 9.484
%R 10.1172/jci.insight.180667
%X 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-like memory T cells within this subset. In addition, after vaccination T cells lacking known memory markers and functionally resembling genuine naive T cells were identified, referred to herein as marker-negative T (TMN) cells. 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 uncover additional complexity within the post-immune T cell compartment and implicate TMN cells in durable immune responses.