Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Center for Molecular Medicine, 17176 Stockholm, Sweden.
Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, 17176 Stockholm, Sweden.
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.
T 细胞在遇到抗原后会分化为具有不同功能的状态。这些状态由用于鼠类和人类 T 细胞的不同细胞表面标志物来区分，这阻碍了 T 细胞特性的跨物种转化。我们旨在确定反映 CD8 T 细胞分化程度的表面标志物，并描绘出小鼠和人类中功能可比的状态。CITEseq 分析表明，趋化因子受体 CX3CR1 的表达与 CD8 T 细胞分化梯度呈梯度表达相关。CX3CR1 表达区分了人类和小鼠的 CD8 和 CD4 T 细胞状态，这是通过迁移和功能特性来定义的。用 CD62L 细化的分级 CX3CR1 表达准确地捕获了高维 T 细胞分化连续体。此外，CX3CR1 表达梯度描绘了在稳定状态下以及在两种物种的纵向跟踪的病毒特异性 CD8 T 细胞中具有可比特性的状态。因此，分级 CX3CR1 表达提供了一种策略，可以在跨物种的情况下转化不同 T 细胞分化状态的行为。
