| Budget Amount *help |
¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2002: ¥600,000 (Direct Cost: ¥600,000)
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| Research Abstract |
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.
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