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.
Endo
Yukie
Y
Department of Dermatology, Gunma University Graduate School of Medicine, 3-39-22 Showa machi, Maebashi Gunma 371-8511, Japan.
Ishikawa
Osamu
O
Negishi
Izumi
I
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology; D002452:Cell Count; D049109:Cell Proliferation; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D003208:Concanavalin A / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology* / Q000502:physiology*; D000078404:Epidermal Cells; D015870:Gene Expression; D007376:Interleukin-2 / Q000235:genetics; D037181:Lectins, C-Type; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000378:metabolism; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000502:physiology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000502:physiology*; D051746:ZAP-70 Protein-Tyrosine Kinase; D000099192:CD69 Antigens
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D003208:Concanavalin A; D007376:Interleukin-2; D037181:Lectins, C-Type; D009687:Nuclear Proteins; D011505:Protein-Tyrosine Kinases; D016692:Receptors, Antigen, T-Cell, gamma-delta; D051746:ZAP-70 Protein-Tyrosine Kinase; D000099192:CD69 Antigens; C485468:Cd3e protein, mouse; C470953:Thy28 protein, mouse; C497262:Zap70 protein, mouse