Regulation of αβ/γδ, T cell lineage commitment and peripheral T cell responses by Notch/RBP-J signaling
Regulation of αβ/γδ, T cell lineage commitment and peripheral T cell responses by Notch/RBP-J signaling
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DOI：
10.1016/s1074-7613(04)00109-8
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发表时间：
2004-05-01
期刊：
影响因子：
32.4
通讯作者：
Honjo, T
中科院分区：
文献类型：
--
作者：
Tanigaki, K;Tsuji, M;Honjo, T
RBP-J是Notch信号传导的关键介质，其调节大范围的细胞命运决定。为了阐明Notch信号在T细胞发育中的功能，我们通过将RBP-J floxed小鼠与Ick-cre或CD 4-cre转基因小鼠杂交，在T细胞发育的两个阶段特异性地灭活RBP-J。RBP-J在早期发育阶段的丧失导致γ δ T细胞的生成增强和迁移加速，而α T细胞的发育在双阴性3阶段被阻止。后期RBP-J的缺失不影响CD 4或CD 8阳性成熟T细胞的绝对数量或产生率，但增强了Th 1细胞应答，降低了CD 4（+）T细胞增殖。我们的数据表明，Notch/RBP-J信号调节γ δ T细胞的产生和迁移，T细胞的成熟，CD 4（+）T细胞终末分化为Th 1/Th 2细胞，以及T细胞的活化。
RBP-J is a key mediator of Notch signaling that regulates a large spectrum of cell fate determinations. To elucidate the functions of Notch signaling in T cell development, we inactivated RBP-J specifically at two stages of T cell development by crossing RBP-J floxed mice with Ick-cre or CD4-cre transgenic mice. The loss of RBP-J at an earlier developmental stage resulted in enhanced generation and accelerated emigration of gammadelta T cells, whereas alphabeta T cell development was arrested at the double-negative 3 stage. The loss of RBP-J at a later stage did not affect the absolute number or the production rate of CD4 or CD8-positive mature T cells but enhanced Th1 cell response and reduced CD4(+) T cell proliferation. Our data demonstrated that Notch/RBP-J signaling regulates gammadelta T cell generation and migration, up T cell maturation, terminal differentiation of CD4(+) T cells into Th1/Th2 cells, and activation of T cells.