Induction of CCR7 expression in thymocytes requires both ERK signal and Ca(2+) signal

CC chemokine receptor 7 (CCR7) expression is crucial for thymocyte trafficking across the corticomedullary junction in the thymus and for lymph node homing of naive T cells. However, the induction mechanism of CCR7 expression is vastly unknown. In isolated CD4+CD8+CCR7-thymocytes, a moderate 20-h pulse stimulation with a combination of the calcium ionophore ionomycin and the protein kinase C activator phorbol myristate acetate induced CCR7 expression and CD8 downregulation. Similar changes were induced in a CD4+CD8+CCR7- T cell line upon stimulation with the same combination of reagents, but not with either one alone. These changes were inhibited by U0126, an inhibitor of the extracellular signal-regulated kinase kinase (ERKK/MEK). The transfectants expressing a constitutively active form of the MEK kinase Raf-1 became CD4+CD8+CCR7+ upon stimulation with ionomycin alone. Thus, Raf-1-mediated signals and Ca(2+)-dependent signals are essential to induce CCR7 expression in CD4+CD8+ T cells and thymocytes as well as their differentiation.