Two prototypic types of virus-specific CD8+ T cells can be found in latently infected individuals: CD45R0+ CD27+ CCR7− effector-memory, and CD45RA+ CD27− CCR7− effector-type cells. It has recently been implied that CD45RA+ CD27− CCR7− T cells are terminally differentiated effector cells and as such have lost all proliferative capacity. We show in this study, however, that stimulation of CMV-specific CD45RA+ CD27− CCR7− T cells with their cognate peptide in concert with either CD4+ help or IL-2, IL-15, or IL-21 in fact induces massive clonal expansion. Concurrently, these stimulated effector T cells change cell surface phenotype from CD45RA to CD45R0 and regain CCR7, while effector functions are maintained. Our data imply that CD45RA+ CD27− CCR7− effector-type T cells contribute to immunity not only by direct execution of effector functions, but also by yielding progeny in situations of viral reinfection or reactivation.