Zeta-chain-associated protein-70 molecule is essential for the proliferation and the final maturation of dendritic epidermal T cells.

Adult murine epidermis contains members of the epithelial gammadelta T-cell family called dendritic epidermal T cells (DETCs). Their development and maturation have been the 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 alphabeta T cells. In mice lacking ZAP-70, thymic development of alphabeta T cells was completely arrested at the immature CD4(+)CD8(+) TCR(low) stage. Here, we examined whether or not the development and maturation of DETCs were altered in ZAP-70-deficient mice. Immunohistochemical analyses of epidermal sheets revealed that the number of DETCs was reduced and their characteristic dendrites were lost or markedly shortened in ZAP-70(-/-) mice. In flow cytometric analyses, the expression levels of gammadelta TCR and Thy-1.2 on the ZAP-70(-/-) DETCs were lower than those on ZAP-70(+/-) DETCs. The expression of a very early activation antigen, CD69, was not detected on ZAP-70(-/-) DETCs, whereas CD69 was expressed on ZAP-70(+/-) DETCs. Furthermore, ZAP-70(-/-) DETCs showed markedly reduced proliferation and no IL-2 gene expression in response to anti-CD3epsilon or concanavalin A stimulation. These results suggest that ZAP-70 is essential for TCR signaling which induces the proliferation and the final maturation of DETCs in the epidermis.