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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Zwijnenburg AJ, Pokharel J, Varnaitė R, Zheng W, Hoffer E, Shryki I, Comet NR, Ehrström M, Gredmark-Russ S, Eidsmo L, Gerlach C

Immunity 56 (8) 1955-1974.e10 [2023-08-08; online 2023-07-24]

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.

Bioinformatics Support for Computational Resources [Service]

NGI Stockholm (Genomics Production) [Service]

National Genomics Infrastructure [Service]

PubMed 37490909

DOI 10.1016/j.immuni.2023.06.025

Crossref 10.1016/j.immuni.2023.06.025

pii: S1074-7613(23)00282-0