The cellular microenvironment regulates CX3CR1 expression on CD8+ T cells and the maintenance of CX3CR1+ CD8+ T cells

Eur J Immunol. 2024 Jan;54(1):e2350658. doi: 10.1002/eji.202350658. Epub 2023 Oct 19.


Expression levels of the chemokine receptor CX3CR1 serve as high-resolution marker delineating functionally distinct antigen-experienced T-cell states. The factors that influence CX3CR1 expression in T cells are, however, incompletely understood. Here, we show that in vitro priming of naïve CD8+ T cells failed to robustly induce CX3CR1, which highlights the shortcomings of in vitro priming settings in recapitulating in vivo T-cell differentiation. Nevertheless, in vivo generated memory CD8+ T cells maintained CX3CR1 expression during culture. This allowed us to investigate whether T-cell receptor ligation, cell death, and CX3CL1 binding influence CX3CR1 expression. T-cell receptor stimulation led to downregulation of CX3CR1. Without stimulation, CX3CR1+ CD8+ T cells had a selective survival disadvantage, which was enhanced by factors released from necrotic but not apoptotic cells. Exposure to CX3CL1 did not rescue their survival and resulted in a dose-dependent loss of CX3CR1 surface expression. At physiological concentrations of CX3CL1, CX3CR1 surface expression was only minimally reduced, which did not hamper the interpretability of T-cell differentiation states delineated by CX3CR1. Our data further support the broad utility of CX3CR1 surface levels as T-cell differentiation marker and identify factors that influence CX3CR1 expression and the maintenance of CX3CR1 expressing CD8+ T cells.

Keywords: CD8 T cell; CX3CL1; CX3CR1; Memory.

MeSH terms

  • CD8-Positive T-Lymphocytes* / metabolism
  • CX3C Chemokine Receptor 1 / metabolism
  • Cellular Microenvironment
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Chemokine* / genetics


  • Receptors, Chemokine
  • Receptors, Antigen, T-Cell
  • CX3C Chemokine Receptor 1