Study on dendritic epidermal T cells in mice

小鼠树突状表皮T细胞的研究

• 批准号: 14570797
• 负责人: NEGISHI Izumi
• 金额: $ 0.83万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570797/
• 关键词: ZAP-70; DETC; γδ T cell; T cell differentiation; differentiation; maturation and differentiation

Adult murine epidermis contains members of the epithelial γδ T-cell family called dendritic epidermal T cells (DETC). Their development and maturation have been subjects of investigations, but the details are still unclear. T cell receptor (TCR) zeta-chain associated protein-70 (ZAP-70), one of the protein tyrosine kinases required for TCR signaling, plays a pivotal role in the development of αβ T cells. In mice lacking ZAP-70, thymic development of αβ T cells was completely arrested at the immature CD4^+CD8^+ TCR^<low> stage. Here, we examined whether or not development and maturation of DETC were altered in ZAP-70-deficient mice. Immunohistochemical analyses of epidermal sheets revealed that the number of DETC was reduced and their characteristic dendrites were lost or markedly shortened in ZAP-70^<-/-> mice. In flow cytometric analyses, the expression levels of γδ TCR and Thy-1.2 on ZAP-70^<-/-> DETC were lower than those on ZAP-70^<+/-> DETC. The expression of a very early activation antigen, CD69, was hardly detected on the ZAP-70^<-/-> DETC, whereas CD69 positive cells were present in freshly prepared ZAP-70^<+/-> DETC. Furthermore, ZAP-70^<-/-> mice showed markedly reduced DETC proliferation in response to anti-CD3ε stimulation. These results indicate that the TCR signal via ZAP-70 is also essential for the development and the functional maturation of DETC.

成年小鼠表皮含有上皮 γδ T 细胞家族的成员，称为树突状表皮 T 细胞 (DETC)。它们的发育和成熟一直是研究的主题，但细节仍不清楚。 T 细胞受体 (TCR) zeta 链相关蛋白 70 (ZAP-70) 是 TCR 信号传导所需的蛋白酪氨酸激酶之一，在 αβ T 细胞的发育中发挥着关键作用。在缺乏ZAP-70的小鼠中，αβT细胞的胸腺发育完全停滞在未成熟的CD4^+CD8^+TCR^<低>阶段。在这里，我们检查了 ZAP-70 缺陷小鼠中 DETC 的发育和成熟是否发生改变。表皮层的免疫组织化学分析表明，ZAP-70^-/- 小鼠中 DETC 的数量减少，其特征性树突丢失或显着缩短。流式细胞术分析发现，ZAP-70^<-/->DETC上γδTCR和Thy-1.2的表达水平低于ZAP-70^<+/->DETC上的表达水平。在ZAP-70^-/-DETC上几乎检测不到极早期激活抗原CD69的表达，而CD69阳性细胞存在于新鲜制备的ZAP-70^+/-DETC中。此外，ZAP-70^-/-小鼠响应抗CD3ε刺激而表现出显着降低的DETC增殖。这些结果表明，通过 ZAP-70 的 TCR 信号对于 DETC 的发育和功能成熟也至关重要。