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

IL-7受体（IL-7R）缺陷小鼠早期淋巴细胞扩张严重受损，缺乏γ - δ T细胞。此外，TCR γ基因的V-J重组在这些突变小鼠中被阻断。为了测试IL-7R对γ - T细胞扩增和/或存活的作用，我们将Vgamma2/Vdelta5转基因引入IL-7R缺陷小鼠。Vgamma2 Tg+ IL-7R+/-小鼠胸腺细胞中有70%以上为转基因γ δ T细胞。相比之下，Vgamma2 Tg+ IL-7R-/-小鼠胸腺中未检测到γ δ T细胞。此外，在Vgamma2 Tg+ IL- 7R-/-脾脏中未观察到明显的γ δ t细胞群。这些数据表明，IL-7R对胸腺和脾脏γ δ T细胞的扩增和/或存活至关重要。为了检查胸腺外γ δ t细胞的发育，我们接下来分析了小肠上皮内淋巴细胞（IEL）。引入转基因后，IL-7R-/-小鼠小肠内γ - T细胞数量部分恢复。这些数据表明，IL-7R对于肠内γ - δ t细胞的扩增和/或存活是必不可少的，并且一些其他细胞因子如IL-15可以补充IL-7以支持胸腺外γ - δ t细胞的发育。据报道，引入Bcl-2转基因可恢复il - 7r缺陷小鼠的α T细胞发育。然而，这并没有恢复Vgamma2 Tg+ IL-7R-/-小鼠的γ - T细胞发育。这些结果表明，IL-7R信号在γ δ T细胞的增殖和存活中起作用。

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.