Graded expression of the chemokine receptor CX3CR1 marks differentiation states of human and murine T cells and enables cross-species interpretation

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  • Anthonie Johan Zwijnenburg
  • Jyoti Pokharel
  • Renata Varnaite
  • Zheng, Wenning
  • Elena Hoffer
  • Iman Shryki
  • Natalia Ramirez Comet
  • Marcus Ehrström
  • Sara Gredmark-Russ
  • Eidsmo, Liv
  • Carmen Gerlach
T cells differentiate into functionally distinct states upon antigen encounter. These states are delineated by different cell surface markers for murine and human T cells, which hamper cross-species translation of T cell properties. We aimed to identify surface markers that reflect the graded nature of CD8+ T cell differentiation and delineate functionally comparable states in mice and humans. CITEseq analyses revealed that graded expression of CX3CR1, encoding the chemokine receptor CX3CR1, correlated with the CD8+ T cell differentiation gradient. CX3CR1 expression distinguished human and murine CD8+ and CD4+ T cell states, as defined by migratory and functional properties. Graded CX3CR1 expression, refined with CD62L, accurately captured the high-dimensional T cell differentiation continuum. Furthermore, the CX3CR1 expression gradient delineated states with comparable properties in humans and mice in steady state and on longitudinally tracked virus-specific CD8+ T cells in both species. Thus, graded CX3CR1 expression provides a strategy to translate the behavior of distinct T cell differentiation states across species.
Original languageEnglish
JournalImmunity
Volume56
Issue number8
Pages (from-to)1955-1974e10
ISSN1074-7613
DOIs
Publication statusPublished - 2023

ID: 385022512