Nishijima Ken-Ichi, Ando Munetoshi, Sano Shusuke, Hayashi-Ozawa Aiko, Kinoshita Yoshinori, Iijima Shinji
Department of Biotechnology, Nagoya University, Nagoya, Japan.
Immunology. 2005 Nov;116(3):347-53. doi: 10.1111/j.1365-2567.2005.02234.x.
In this study, we investigated the costimulatory activity of l-selectin in primary mouse T cells. Proliferation induced by immobilized anti-CD3 antibody was enhanced by immobilized anti-l-selectin antibody. In contrast to the anti-CD28 antibody, anti-l-selectin antibody did not enhance interleukin-2 (IL-2) expression. One of the cyclin-dependent kinase (cdk) inhibitors, p27, was reduced by costimulation with anti-l-selectin antibody, as with anti-CD28 antibody, suggesting that the enhancement of T-cell proliferation is the result of a reduced p27 level. Since anti-l-selectin antibody enhanced the activation of extracellular signal-regulated protein kinase (ERK) induced by anti-CD3 antibody, ERK plays an important role in signal integration during costimulation. These results suggest that the mechanism of T-cell costimulation is at least partially different between CD28 and l-selectin, although the two mechanisms share a common downstream event, a reduction of p27 level, as a critical biochemical event in the cell cycle progression of T cells.
在本研究中，我们调查了L-选择素在原代小鼠T细胞中的共刺激活性。固定化抗L-选择素抗体增强了固定化抗CD3抗体诱导的增殖。与抗CD28抗体不同，抗L-选择素抗体未增强白细胞介素-2（IL-2）的表达。细胞周期蛋白依赖性激酶（cdk）抑制剂之一p27，与抗CD28抗体一样，通过抗L-选择素抗体共刺激而降低，这表明T细胞增殖的增强是p27水平降低的结果。由于抗L-选择素抗体增强了抗CD3抗体诱导的细胞外信号调节蛋白激酶（ERK）的激活，ERK在共刺激过程中的信号整合中起重要作用。这些结果表明，尽管CD28和L-选择素的两种共刺激机制共享一个共同的下游事件，即p27水平降低，作为T细胞细胞周期进程中的关键生化事件，但它们之间的T细胞共刺激机制至少部分不同。
