条件性 Efnb1 缺失对 T 细胞发育和功能的影响。
The effect of conditional EFNB1 deletion in the T cell compartment on T cell development and function.
机构信息
Laboratory of Immunology Centre de recherche de Centre hospitalier de l'Université de Montréal, Notre-Dame Hospital, Montreal, Quebec, Canada.
出版信息
BMC Immunol. 2011 Dec 19;12:68. doi: 10.1186/1471-2172-12-68.
BACKGROUND
Eph kinases are the largest family of cell surface receptor tyrosine kinases. The ligands of Ephs, ephrins (EFNs), are also cell surface molecules. Ephs interact with EFNs transmitting signals in both directions, i.e., from Ephs to EFNs and from EFNs to Ephs. EFNB1 is known to be able to co-stimulate T cells in vitro and to modulate thymocyte development in a model of foetal thymus organ culture. To further understand the role of EFNB1 in T cell immunity, we generated T-cell-specific EFNB1 gene knockout mice to assess T cell development and function in these mice.
RESULTS
The mice were of normal size and cellularity in the thymus and spleen and had normal T cell subpopulations in these organs. The bone marrow progenitors from KO mice and WT control mice repopulated host spleen T cell pool to similar extents. The activation and proliferation of KO T cells was comparable to that of control mice. Naïve KO CD4 cells showed an ability to differentiate into Th1, Th2, Th17 and Treg cells similar to control CD4 cells.
CONCLUSIONS
Our results suggest that the function of EFNB1 in the T cell compartment could be compensated by other members of the EFN family, and that such redundancy safeguards the pivotal roles of EFNB1 in T cell development and function.
背景
Eph 激酶是细胞表面受体酪氨酸激酶家族中最大的家族。Eph 的配体，即 Ephrins（EFNs），也是细胞表面分子。Ephs 与 EFNs 相互作用，双向传递信号，即 Ephs 向 EFNs 传递信号，EFNs 向 Ephs 传递信号。已知 EFNB1 能够在体外刺激 T 细胞，并在胎胸腺器官培养模型中调节胸腺细胞发育。为了进一步了解 EFNB1 在 T 细胞免疫中的作用，我们生成了 T 细胞特异性 EFNB1 基因敲除小鼠，以评估这些小鼠中 T 细胞的发育和功能。
结果
这些小鼠的胸腺和脾脏大小和细胞数量正常，且这些器官中的 T 细胞亚群正常。来自 KO 小鼠和 WT 对照小鼠的骨髓祖细胞以相似的程度重新填充宿主脾脏 T 细胞池。KO T 细胞的激活和增殖与对照小鼠相当。幼稚的 KO CD4 细胞显示出与对照 CD4 细胞相似的分化为 Th1、Th2、Th17 和 Treg 细胞的能力。
结论
我们的结果表明，EFNB1 在 T 细胞区室中的功能可以被 EFN 家族的其他成员所补偿，这种冗余性保障了 EFNB1 在 T 细胞发育和功能中的关键作用。
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