Defective signaling in a subpopulation of CD4+ T cells in the absence of Ca2+/calmodulin-dependent protein kinase IV
Defective signaling in a subpopulation of CD4+ T cells in the absence of Ca2+/calmodulin-dependent protein kinase IV
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DOI：
10.1128/mcb.22.1.23-29.2002
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发表时间：
2002-01-01
影响因子：
5.3
通讯作者：
Means, AR
中科院分区：
文献类型：
--
作者：
Anderson, KA;Means, AR
钙/钙调素依赖的蛋白激酶IV缺陷(CaMKIV-/-)小鼠已被用来研究该酶在CD4(+)T细胞中的作用。我们确定了一个亚群的CD4(+)T细胞的功能缺陷，其特征是记忆表型的CD4(+)T细胞的细胞表面标志物特征。一旦T细胞受体结合，突变细胞产生的白介素2(IL-2)、白介素4和γ干扰素蛋白和信使核糖核酸水平降低。该缺陷继发于不能磷酸化CREB和诱导依赖CREB的即刻早期基因，包括细胞因子基因诱导所必需的c-Jun、FosB、FRA2和JunB。相比之下，来自CaMKIV-/-小鼠的受刺激的初始CD4(+)T细胞表现出正常的CREB磷酸化、即刻早期基因的诱导和细胞因子的产生。因此，除了定义CaMKIV在T细胞亚群中的重要信号作用外，我们还确定了幼稚T细胞和表达记忆表型特征的细胞表面标记的T细胞之间对细胞因子产生的差异信号要求。
Ca2+/calmodulin-dependent protein kinase IV-deficient (CaMKIV-/-) mice have been used to investigate the role of this enzyme in CD4(+) T cells. We identify a functional defect in a subpopulation of CD4(+) T cells, characterized by a cell surface marker profile usually found on memory phenotype CD4(+) T cells. Upon T-cell receptor engagement, the mutant cells produce diminished levels of interleukin-2 (IL-2), IL-4, and gamma interferon protein and mRNA. The defect is secondary to an inability to phosphorylate CREB and to induce CREB-dependent immediate-early genes, including c-jun, fosB, fra2, and junB, which are required for cytokine gene induction. In contrast, stimulated naive CD4(+) T cells from CaMKIV-/- mice show normal CREB phosphorylation, induction of immediate-early genes, and cytokine production. Thus, in addition to defining an important signaling role for CaMKIV in a subpopulation of T cells, we identify differential signaling requirements for cytokine production between naive T cells and T cells that express cell surface markers characteristic of the memory phenotype.