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

Immunity. 2023 Aug 8;56(8):1955-1974.e10. doi: 10.1016/j.immuni.2023.06.025. Epub 2023 Jul 24.


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.

Keywords: CD8 T cell; CX3CR1; T cell; differentiation; differentiation marker; memory; response to infection; subsets; viral infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes*
  • CX3C Chemokine Receptor 1 / genetics
  • CX3C Chemokine Receptor 1 / metabolism
  • Cell Differentiation
  • Humans
  • Immunologic Memory
  • Mice
  • Receptors, Chemokine*


  • CX3C Chemokine Receptor 1
  • CX3CR1 protein, human
  • Receptors, Chemokine
  • Cx3cr1 protein, mouse