Maki K, Sunaga S, Komagata Y, Kodaira Y, Mabuchi A, Karasuyama H, Yokomuro K, Miyazaki J I, Ikuta K
Department of Disease-Related Gene Regulation Research (Sandoz) Faculty of Medicine, The Univerisity of Tokyo, Japan.
Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7172-7. doi: 10.1073/pnas.93.14.7172.
The interleukin 7 receptor (IL-7R) plays a crucial role in early B- and T-cell development. It consists of a unique a chain and a common gamma chain [IL-2 receptor gamma chain (IL-2Rgamma)]. Gene inactivation of IL-7, IL-7R, and IL-2Rgamma resulted in severe impairment of B and T lymphopoiesis in mice. In addition, IL-2Rgamma-deficient mice lack gammadelta T cells in the skin and have the impaired development of natural killer (NK) cells and intraepithelial lymphocytes. To explore the role of IL-7/IL-7R system in gammadelta T- and NK-cell development, we have generated and analyzed IL-7R-deficient mice. gammadelta T cells were absent from skin, gut, liver, and spleen in the deficient mice. In contrast, alphabeta T and B cells were detected in reduced, but certain, numbers, and NK cells developed normally. The gammadelta T-cell development in fetal and adult thymus was also completely blocked. These results clearly demonstrate that the signal from IL-7R is indispensable for gammadelta T-cell development in both thymic and extrathymic pathways. On the contrary, it is suggested that NK-cell development requires cytokine(s) other than IL-7.
白细胞介素7受体(IL-7R)在B细胞和T细胞早期发育中起关键作用。它由一条独特的α链和一条共同的γ链[白细胞介素2受体γ链(IL-2Rγ)]组成。IL-7、IL-7R和IL-2Rγ的基因失活导致小鼠B淋巴细胞生成和T淋巴细胞生成严重受损。此外,IL-2Rγ缺陷小鼠的皮肤中缺乏γδT细胞,自然杀伤(NK)细胞和上皮内淋巴细胞的发育也受到损害。为了探究IL-7/IL-7R系统在γδT细胞和NK细胞发育中的作用,我们培育并分析了IL-7R缺陷小鼠。缺陷小鼠的皮肤、肠道、肝脏和脾脏中均不存在γδT细胞。相比之下,αβT细胞和B细胞数量减少但仍可检测到,NK细胞发育正常。胎儿和成年胸腺中的γδT细胞发育也完全受阻。这些结果清楚地表明,IL-7R发出的信号对于胸腺途径和胸腺外途径中的γδT细胞发育都是不可或缺的。相反,有人提出NK细胞的发育需要IL-7以外的细胞因子。