Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA, USA.
Blood. 2010 Dec 16;116(25):5548-59. doi: 10.1182/blood-2010-06-292748. Epub 2010 Sep 16.
SH2 domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76) nucleates a signaling complex critical for T-cell receptor (TCR) signal propagation. Mutations in the tyrosines of SLP-76 result in graded defects in TCR-induced signals depending on the tyrosine(s) affected. Here we use 2 strains of genomic knock-in mice expressing tyrosine to phenylalanine mutations to examine the role of TCR signals in the differentiation of effector and memory CD8(+) T cells in response to infection in vivo. Our data support a model in which altered TCR signals can determine the rate of memory versus effector cell differentiation independent of initial T-cell expansion. Furthermore, we show that TCR signals sufficient to promote CD8(+) T-cell differentiation are different from those required to elicit inflammatory cytokine production.
SH2 结构域富含白细胞磷酸蛋白 76kDa（SLP-76）可形成一个信号复合物，对 T 细胞受体（TCR）信号转导至关重要。SLP-76 酪氨酸的突变导致 TCR 诱导信号的逐渐缺陷，这取决于受影响的酪氨酸。在这里，我们使用 2 种表达酪氨酸到苯丙氨酸突变的基因组敲入小鼠品系，研究 TCR 信号在体内感染时对效应器和记忆 CD8+T 细胞分化的作用。我们的数据支持这样一种模型，即改变的 TCR 信号可以决定记忆与效应细胞分化的速度，而与初始 T 细胞扩增无关。此外，我们还表明，促进 CD8+T 细胞分化所需的 TCR 信号与引发炎症细胞因子产生所需的信号不同。
