Study on dendritic epidermal T cells in mice

成年鼠表皮含有上皮γδ T细胞家族的成员，称为树突状表皮T细胞（DETC）。它们的发展和成熟一直是调查的主题，但细节仍然不清楚。T细胞受体（TCR）ζ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细胞的发育中起着关键作用。在缺乏ZAP-70的小鼠中，αβ T细胞的胸腺发育完全停滞在未成熟的CD 4 ^+ CD 8 ^+ TCR^<low>阶段。在这里，我们研究了在ZAP-70缺陷小鼠中DETC的发育和成熟是否改变。表皮片的免疫组织化学分析显示，在ZAP-70^&lt;-/-&gt;小鼠中，DETC的数量减少，其特征性树突丢失或显著缩短。流式细胞术分析显示，ZAP-70^&lt;-/-&gt; DETC上γδ TCR和Thy-1.2的表达水平低于ZAP-70^&lt;+/-&gt; DETC上的γδ TCR和Thy-1.2的表达水平。在ZAP-70^&lt;-/-&gt; DETC上几乎检测不到非常早期活化抗原CD 69的表达，而在新鲜制备的ZAP-70^&lt;+/-&gt; DETC中存在CD 69阳性细胞。此外，ZAP-70^&lt;-/-&gt;小鼠显示出响应于抗CD 3 ε刺激的DETC增殖显著降低。这些结果表明，TCR信号通过ZAP-70也是必不可少的DETC的发展和功能成熟。

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.