Department of Medical Genetics, Ullevaal University Hospital, Kirkeveien 166, 0407 Oslo, Norway.
J Leukoc Biol. 2010 Jun;87(6):1059-68. doi: 10.1189/jlb.0709497. Epub 2010 Feb 16.
We have demonstrated previously that binding of ephrin-A1 to EphA receptors on human CD4(+) and CD8(+) T cells stimulates migration. Two EphA receptors have been reported in T cells: EphA1 at the protein level and EphA4 at the mRNA level. In this study, we wanted to investigate the expression profile of these receptors in T cell subpopulations and to test if expression differences would affect the potential of cells to migrate upon ephrin-A1 binding. We have generated an anti-EphA4 mAb for expression analysis. Our data show that functional EphA4 is expressed on the cell surface of CD4(+) and CD8(+) T cells. In addition, EphA4 receptor expression is induced after overnight incubation in serum-free medium, in particular, on CD4(+)CD45RO(+) T cells. Migration of CD4(+) T cells in response to ephrin-A1 is observed for memory cells (CD45RO(+)) and much weaker for naïve cells (CD45RA(+)). A signaling complex associated with the EphA4 receptor has also been isolated and includes EphA1, the Src family kinases Fyn and Lck, Slp76, and Vav1. To conclude, T cells express EphA1 and EphA4 receptors. Expression differences of EphA4 are observed in subpopulations of CD4(+) T cells. This is related to the cell migration potential after ephrin-A1 binding.
我们之前已经证明，人源 CD4(+)和 CD8(+)T 细胞上的 Ephrin-A1 与 EphA 受体结合会刺激细胞迁移。在 T 细胞中已经报道了两种 EphA 受体：EphA1 在蛋白水平，EphA4 在 mRNA 水平。在这项研究中，我们希望研究这些受体在 T 细胞亚群中的表达谱，并测试表达差异是否会影响细胞在 Ephrin-A1 结合时迁移的潜力。我们已经生成了用于表达分析的抗 EphA4 mAb。我们的数据表明，功能性 EphA4 表达在 CD4(+)和 CD8(+)T 细胞的细胞表面上。此外，在无血清培养基中孵育过夜后，EphA4 受体表达被诱导，特别是在 CD4(+)CD45RO(+)T 细胞上。Ephrin-A1 诱导 CD4(+)T 细胞迁移，观察到记忆细胞（CD45RO(+))和较弱的幼稚细胞（CD45RA(+))。还分离出与 EphA4 受体相关的信号复合物，该复合物包括 EphA1、Src 家族激酶 Fyn 和 Lck、Slp76 和 Vav1。总之，T 细胞表达 EphA1 和 EphA4 受体。在 CD4(+)T 细胞亚群中观察到 EphA4 的表达差异。这与 Ephrin-A1 结合后细胞迁移的潜力有关。
