Analysis of lymphpcyte differentiation and growth mechanism by IL-7 receptor deficient mice

IL-7受体缺陷小鼠淋巴细胞分化及生长机制分析

基本信息

批准号：
09836005
负责人：
IKUTA Koichi
金额：
$ 2.05万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09836005/
关键词：
IL-7 receptor Bcl-2 gammadelta T cell transgenic mouse サイトカイン T細胞

项目摘要

IL-7 receptor (IL-7R)-deficient mice have severely impaired expansion of early lymphocytes and lack gammadelta T cells. In addition, the V-J recombination of TCR gamma genes is blocked in these mutant mice. To test the role of IL-7R on expansion and/or survival of gammadelta T cells irrespective of the recombination, we introduced a Vgamma2/Vdelta5 transgene into the IL-7R-deficient mice. More than 70% of thymocytes were transgenic gammadelta T cells in Vgamma2 Tg+ IL-7R+/- mice. In contrast, gammadelta T cells were not detected in the thymus of Vgamma2 Tg+ IL-7R-/- mice. In addition, no distinct gammadelta T-cell population was observed in Vgamma2 Tg+ IL- 7R-/- spleen. These data demonstrated that IL-7R is crucial for the expansion and/or survival of gammadelta T cells in the thymus and spleen. To examine the extrathymic gammadelta T-cell development, we next analyzed intraepithelial lymphocytes (IEL) in the small intestine. Cell numbers of gammadelta T cells were partially restored in the small intestine of IL-7R-/- mice by introduction of the transgene. These data demonstrated that IL-7R is dispensable for the expansion and/or survival of gammadelta IEL in the intestine and that some other cytokine like IL-15 can complement IL-7 to support extrathymic gammadelta T-cell development.It has been reported that the introduction of Bcl-2 transgenes restore alphabeta T cell development in IL-7R-deficient mice. However, this did not restore gammadelta T cell development in Vgamma2 Tg+ IL-7R-/- mice. These results suggested that IL-7R signaling plays a role in the proliferation of gammadelta T cells as well as their survival.

IL-7受体（IL-7R）缺陷小鼠的早期淋巴细胞的扩张严重损害，缺乏γTELTATT细胞。另外，在这些突变小鼠中，TCR伽马基因的V-J重组被阻断。为了测试IL-7R在伽马去氏菌T细胞膨胀和/或存活中的作用，而与重组无关，我们将vgamma2/vdelta5 transgene引入了IL-7R缺乏的小鼠中。在VGAMMA2 TG+ IL-7R +/-小鼠中，超过70％的胸腺细胞是转基因γT细胞。相比之下，在Vgamma2 Tg+ IL-7R - / - 小鼠的胸腺中未检测到γT细胞。此外，在VGAMMA2 TG+ IL-7R - / - 脾脏中未观察到明显的γT-T细胞种群。这些数据表明，IL-7R对于胸腺和脾脏中γT细胞的膨胀和/或存活至关重要。为了检查外肌外γT-T细胞的发育，我们接下来分析了小肠中的上皮内淋巴细胞（IEL）。通过引入转基因，在IL-7R - / - 小鼠的小肠中部分恢复了伽玛达尔塔T细胞的细胞数。 These data demonstrated that IL-7R is dispensable for the expansion and/or survival of gammadelta IEL in the intestine and that some other cytokine like IL-15 can complement IL-7 to support extrathymic gammadelta T-cell development.It has been reported that the introduction of Bcl-2 transgenes restore alphabeta T cell development in IL-7R-deficient mice.但是，这并未恢复VGAMMA2 TG+ IL-7R - / - 小鼠中的γT细胞发育。这些结果表明，IL-7R信号传导在γT细胞的增殖以及它们的存活中起作用。