G1/S cell cycle arrest provoked in human T cells by antibody to CD26
G1/S cell cycle arrest provoked in human T cells by antibody to CD26
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DOI：
10.1046/j.1365-2567.2002.01510.x
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发表时间：
2002-11-01
期刊：
影响因子：
6.4
通讯作者：
Morimoto, C
中科院分区：
文献类型：
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作者：
Ohnuma, K;Ishii, T;Morimoto, C
CD 26是位于其胞外区的具有二肽基肽酶IV（DPPIV）酶活性的T细胞共刺激分子。CD 26的表达在T细胞活化后增强，而其在静息状态下优先在CD 4（+）记忆T细胞的亚群上表达。在本文中，我们证明了可溶性抗CD 26单克隆抗体（mAb）1F 7的结合抑制人T细胞的生长和增殖，在CD 26转染的Jurkat T细胞系和人T细胞克隆诱导G1/S阻滞，这是与增强p21（Cip 1），表达。这种作用取决于CD 26分子的DPPIV酶活性。此外，我们发现，用抗CD 26 mAb 1F 7处理后，p21（Cip 1）的表达似乎是通过激活细胞外信号调节激酶（ERK）途径诱导的。因此，这些数据表明抗CD 26治疗可能在涉及活化T细胞失调的临床环境中具有潜在用途，包括自身免疫性疾病和移植物抗宿主病。宿主疾病
CD26 is T cell costimulatory molecule with dipeptidyl peptidase IV (DPPIV) enzyme activity located in its extracellular region. The expression of CD26 is enhanced after activation of T cells, while it is preferentially expressed on a subset of CD4(+) memory T cells in the resting state. In this paper, we demonstrate that binding of the soluble anti-CD26 monoclonal antibody (mAb) 1F7 inhibits human T-cell growth and proliferation in both CD26-transfected Jurkat T-cell lines and human T-cell clones by inducing G1/S arrest, which is associated with enhancement of p21(Cip1), expression. This effect depends on the DPPIV enzyme activity of the CD26 molecule. Moreover, we show that expression of p21(Cip1) after treatment with the anti-CD26 mAb 1F7 appears to be induced through activation of extracellular signal-regulated kinase (ERK) pathway. These data thus suggest that anti-CD26 treatment may have potential use in the clinical setting involving activated T cell dysregulation, including autoimmune disorders and graft-vs.-host disease.