Preservation of Naive-phenotype CD4+ T Cells After Vaccination Contributes to Durable Immunity

Overview

Journal JCI Insight

Specialties Biomedical Engineering
General Medicine

Date 2024 Jun 11

PMID 38861490

Authors

Yi-Gen Pan

Laurent Bartolo

Ruozhang Xu

Bijal V Patel

Veronika I Zarnitsyna

Laura F Su

Affiliations

Soon will be listed here.

Abstract

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.

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