Study on dendritic epidermal T cells in mice

2003 Fiscal Year Final Research Report Summary

• Project/Area Number: 14570797
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Dermatology
• Research Institution: Gunma University
• Principal Investigator: NEGISHI Izumi Gunma University, School of Medicine, Department of Dermatology, Assistant professor, 医学部, 講師 (60292611)
• Project Period (FY): 2002 – 2003
• Keywords: ZAP-70 / DETC / γδ T cell / T cell differentiation

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.