<br>细胞微环境调节 CD8+ T 细胞上 CX3CR1 的表达以及 CX3CR1+ CD8+ T 细胞的维持,European Journal of Immunology

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细胞微环境调节 CD8+ T 细胞上 CX3CR1 的表达以及 CX3CR1+ CD8+ T 细胞的维持
European Journal of Immunology ( IF 4.5 ) Pub Date : 2023-10-10 , DOI: 10.1002/eji.202350658
Jyoti Pokharel ₁ , Iman Shryki ₁ , Anthonie J Zwijnenburg ₁ , Ioana Sandu ₁ , Laura Krumm ₁ , Christina Bekiari ₁ , Victor Avramov ₁ , Rebecka Heinbäck ₁ , Josefin Lysell ₂ , Liv Eidsmo _{1,

3} , Helena E Harris ₁ , Carmen Gerlach ₁

Affiliation

趋化因子受体 CX3CR1 的表达水平可作为高分辨率标记，描绘功能上不同的抗原经历的 T 细胞状态。然而，影响 T 细胞中 CX3CR1 表达的因素尚不完全清楚。在这里，我们表明，幼稚 CD8 ⁺ T 细胞的体外启动未能强烈诱导 CX3CR1，这突出了体外启动设置在重现体内 T 细胞分化方面的缺点。尽管如此，体内产生的记忆CD8 ⁺ T细胞在培养过程中仍保持CX3CR1表达。这使我们能够研究 T 细胞受体连接、细胞死亡和 CX3CL1 结合是否影响 CX3CR1 表达。 T 细胞受体刺激导致 CX3CR1 下调。在没有刺激的情况下，CX3CR1 ⁺ CD8 ⁺ T 细胞具有选择性生存劣势，这种劣势会被坏死细胞释放的因子增强，但凋亡细胞不会。暴露于 CX3CL1 并不能挽救它们的生存，并导致 CX3CR1 表面表达呈剂量依赖性丧失。在 CX3CL1 的生理浓度下，CX3CR1 表面表达仅最低限度地降低，这并不妨碍 CX3CR1 描绘的 T 细胞分化状态的可解释性。我们的数据进一步支持 CX3CR1 表面水平作为 T 细胞分化标记物的广泛用途，并确定了影响 CX3CR1 表达和维持表达 CX3CR1 的 CD8 ⁺ T 细胞的因素。

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

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.

更新日期：2023-10-10

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