Shimamura Michio, Huang Yi-Ying, Migishima Rika, Yokoyama Minesuke, Saitoh Takako, Yamamura Takashi
Developmental Immunology Unit, Mitsubishi Kagaku Institute of Life Sciences, Japan.
Immunol Lett. 2008 Nov 16;121(1):38-44. doi: 10.1016/j.imlet.2008.08.002. Epub 2008 Sep 27.
Previously, we found that more than a half of the NK1.1(+) T cell lines prepared from CD1(-/-) livers expressed invariant Valpha19-Jalpha33 TCR alpha chains. Over-expression of the invariant Valpha19-Jalpha33 TCR alpha transgene (Tg) with a natural TCR alpha promoter and an enhancer in mice induced the development of NK1.1(+) T cells (Valpha19 NKT cells) in the lymphoid organs, especially in the liver. Preferential usage of the Valpha19 Tg by NKT cells in the transgenic mouse livers was indirectly indicated by the observation that few NK1.1(+) TCRalphabeta(+) cells of the Valpha19 Tg livers were stained with a cocktail of anti-TCR Valpha antibodies in the FACS analysis. Upon invariant TCR engagement in vivo following injection of mice with anti-CD3 antibody, NKT cells of the Tg mouse livers as well as spleens promptly produced immunoregulatory cytokines such as IL-4 and IFN-gamma and altered surface receptor expression. Collectively, localization of Valpha19 NKT cells in the liver is suggested that are ready to immediately response against antigen stimulation.
此前，我们发现从CD1(-/-)肝脏制备的超过半数的NK1.1(+) T细胞系表达恒定的Valpha19-Jalpha33 TCRα链。在小鼠中用天然TCRα启动子和增强子过表达恒定的Valpha19-Jalpha33 TCRα转基因（Tg）诱导了淋巴器官中NK1.1(+) T细胞（Valpha19 NKT细胞）的发育，尤其是在肝脏中。通过在FACS分析中观察到Valpha19 Tg肝脏中很少有NK1.1(+) TCRalphabeta(+)细胞被抗TCR Valpha抗体混合物染色，间接表明了转基因小鼠肝脏中的NKT细胞优先使用Valpha19 Tg。在用抗CD3抗体注射小鼠后，体内恒定TCR被激活时，Tg小鼠肝脏以及脾脏中的NKT细胞迅速产生免疫调节细胞因子，如IL-4和IFN-γ，并改变表面受体表达。总体而言，Valpha19 NKT细胞在肝脏中的定位表明它们随时准备对抗抗原刺激做出即时反应。
