JNK2 is required for efficient T-cell activation and apoptosis but not for normal lymphocyte development
JNK2 is required for efficient T-cell activation and apoptosis but not for normal lymphocyte development
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DOI：
10.1016/s0960-9822(99)80065-7
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发表时间：
1999-02-11
期刊：
影响因子：
9.2
通讯作者：
Karin, M
中科院分区：
文献类型：
--
作者：
Sabapathy, K;Hu, YL;Karin, M
背景资料：Jun N末端激酶（JNK）信号通路与细胞增殖和凋亡有关，但其功能依赖于细胞类型和诱导信号。在T细胞，JNK已牵连在抗原诱导的活化和apoptosis. Results：我们产生的小鼠缺乏JNK2同工酶。突变小鼠是健康的和可生育的，但缺陷的外周T细胞活化诱导的抗体的CD3组分的T细胞受体（TCR）复合物的增殖和生产的白细胞介素-2（IL-2），IL-4和干扰素-γ（IFN-γ）减少。外源性IL-2可使细胞增殖缺陷得到恢复。B细胞活化在JNK2不存在下是正常的。激活诱导的外周T细胞凋亡在突变型和野生型小鼠之间相当，但缺乏JNK2的未成熟（CD4（+）CD8（+））胸腺细胞对体内给予抗CD3抗体诱导的凋亡具有抗性。JNK 2的缺失也导致了胸腺细胞对CDS抗体的部分抵抗，但对Fas抗体、地塞米松或紫外线C（UVC）诱导的细胞凋亡几乎没有影响。结论：JNK 2是有效激活外周血T细胞而不是B细胞所必需的。外周T细胞活化可能是体内抗CD3抗体给药诱导胸腺细胞凋亡所间接需要的。JNK2以细胞类型特异性和刺激依赖性的方式发挥作用，是抗CD3抗体诱导的未成熟胸腺细胞凋亡所必需的，而不是抗Fas抗体、UVC或地塞米松诱导的凋亡所必需的。JNK2对于成熟T细胞的活化诱导的细胞死亡不是必需的。
Background: The Jun N-terminal kinase (JNK) signaling pathway has been implicated in cell proliferation and apoptosis, but its function seems to depend on the cell type and inducing signal. In T cells, JNK has been implicated in both antigen-induced activation and apoptosis.Results: We generated mice lacking the JNK2 isozymes. The mutant mice were healthy and fertile but defective in peripheral T-cell activation induced by antibody to the CD3 component of the T-cell receptor (TCR) complex proliferation and production of interleukin-2 (IL-2), IL-4 and interferon-gamma (IFN-gamma) were reduced. The proliferation defect was restored by exogenous IL-2. B-cell activation was normal in the absence of JNK2. Activation-induced peripheral T-cell apoptosis was comparable between mutant and wild-type mice, but immature (CD4(+)CD8(+)) thymocytes lacking JNK2 were resistant to apoptosis induced by administration of anti-CD3 antibody in vivo. The lack of JNK2 also resulted in partial resistance of thymocytes to anti-CDS antibody in vitro, but had little or no effect on apoptosis induced by anti-fas antibody, dexamethasone or ultraviolet-C (UVC) radiation.Conclusions: JNK2 is essential for efficient activation of peripheral T cells but not B cells. Peripheral T-cell activation is probably required indirectly for induction of thymocyte apoptosis resulting from administration of anti-CD3 antibody in vivo. JNK2 functions in a cell-type-specific and stimulus-dependent manner, being required for apoptosis of immature thymocytes induced by anti-CD3 antibody but not for apoptosis induced by anti-fas antibody, UVC or dexamethasone. JNK2 is not required for activation-induced cell death of mature T cells.