Duration of calcineurin and Erk signals regulates CD4/CD8 lineage commitment of thymocytes
Duration of calcineurin and Erk signals regulates CD4/CD8 lineage commitment of thymocytes
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DOI：
10.1016/s0008-8749(02)00012-6
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发表时间：
2002-01-01
影响因子：
4.3
通讯作者：
Iwata, M
中科院分区：
文献类型：
--
作者：
Adachi, S;Iwata, M
胸腺细胞的CD4/CD8谱系承诺是由T细胞受体介导的信号控制的，并在体外通过长脉冲刺激分离的CD4(+)CD8(+)胸腺细胞与适当的佛波酯和钙离子载体的组合来模拟。在该培养体系中，与CD8谱系承诺相比，CD4谱系承诺需要更高的细胞内钙离子水平。钙调神经磷酸酶抑制剂FK506在1 nM时抑制胸腺细胞向任一种谱系的发育，而0.3 nM的FK506显著地将胸腺细胞的发育从CD4细胞的命运转变为CD8细胞的命运。在培养开始后8h加入1 nM FK506也可观察到谱系承诺的变化。延迟加入20微米的ERK(ERK)抑制剂U0126也诱导了这种转换。这些结果表明，钙调神经磷酸酶的活性强度以及钙调神经磷酸酶和ERK通路激活的持续时间对胸腺细胞的谱系承诺至关重要。(C)2002年埃尔塞维尔科学公司(美国)。版权所有。
CD4/CD8 lineage commitment of thymocytes is controlled by the T cell receptor-mediated signals and is mimicked in vitro by a long-pulse stimulation of isolated CD4(+)CD8(+) thymocytes with proper combinations of phorbol myristate acetate and the calcium ionophore ionomycin. CD4 lineage commitment required higher intracellular Ca2+ levels than CD8 lineage commitment in this culture system. The calcineurin inhibitor FK506 at 1 nM inhibited the development of thymocytes to either lineage, but 0.3 nM FK506 significantly switched the development from the CD4 cell fate to the CD8 cell fate. The switch in lineage commitment was also observed when 1 nM FK506 was added 8 h after the start of the culture. Delayed addition of 20 muM U0126, an Mek (Erk kinase) inhibitor, also induced the switch. These results suggest that the intensity of calcineurin activity and the duration of both calcineurin and Erk pathway activation are crucial for thymocyte lineage commitment. (C) 2002 Elsevier Science (USA). All rights reserved.