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

• 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

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-7 R）缺陷小鼠早期淋巴细胞的扩增严重受损，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-7 R对γ δ T细胞的扩增和/或存活的作用，无论重组如何，我们将V γ 2/V δ 5转基因引入IL-7 R缺陷小鼠中。在Vgamma 2 Tg+ IL-7 R +/-小鼠中，超过70%的胸腺细胞是转基因γ δ T细胞。相比之下，在V γ 2 Tg+ IL-7 R-/-小鼠的胸腺中未检测到γ δ T细胞。此外，在V γ 2 Tg+ IL-7 R-/-脾中未观察到明显的γ δ T细胞群。这些数据表明，IL-7 R对于胸腺和脾脏中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中的上皮内淋巴细胞（IEL）。通过引入转基因，IL-7 R-/-小鼠小肠中γ δ T细胞的细胞数量部分恢复。这些数据表明，IL-7 R是促进γ δ IEL在肠道中的扩增和/或存活的，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细胞发育。然而，这并没有恢复V γ 2 Tg+ IL-7 R-/-小鼠中的γ δ T细胞发育。这些结果表明，IL-7 R信号传导在γ δ T细胞的增殖以及它们的存活中起作用。

项目成果

Kodaira,Y.: "Antigen-drived clonal accumulation of peritoned γδT cells in vivo." Immundogical Inrestigations. (in press).

Kodaira, Y.：“抗原驱动的体内腹膜 γδT 细胞克隆积累。”（正在出版）。

Uozumi,N.et al.: "Role of cytosolic phospholipase A_2 in allergic response and parturition" Nature. 390. 618-622 (1997)

Uozumi,N.et al.：“胞质磷脂酶 A_2 在过敏反应和分娩中的作用”自然。

Adachi,S.et al.: "Essential role of IL-7 receptor α in the formation of Peyer's patch anlage" Int.Immunol.10. 1-6 (1998)

Adachi, S. 等人：“IL-7 受体 α 在派尔氏斑原基形成中的重要作用”Int.Immunol.1-6 (1998)。

Miyaura, C., et al.: "Increased B-lymphopoiesis by interleukin 7 induces bone loss in mice with intact ovarian function : Similarity to estrogen deficiency." Proc.Natl.Acad.Sci.USA. 94. 9360-9365 (1997)

Miyaura, C. 等人：“白细胞介素 7 增加 B 淋巴细胞生成会导致卵巢功能完整的小鼠骨质流失：与雌激素缺乏相似。”

Sunaga,S.et al.: "Developmentally ordered V-J recombination in mouse T cell receptor γ locus is not perturbed by targeted deletion of the Vγ4 gene" J.Immunol.158. 4223-4228 (1997)

Sunaga, S. 等人：“小鼠 T 细胞受体 γ 基因座中的发育有序 V-J 重组不会因 Vγ4 基因的定向删除而受到干扰”J.Immunol.158 (1997)。