Natural killer (NK) cells have been shown to kill efficiently autologous immature dendritic cells (iDC), while sparing those undergone maturation. In this study we investigated the effect of the interaction between autologous DC and NK-cytolytic T lymphocytes (NK-CTL), a subset of HLA-E-restricted CD8(+) T cells that express HLA class I-specific inhibitory NK receptors. Although these cells share with NK cells various phenotypic and functional features (such as the capacity to lyse most allogeneic, NK-susceptible tumor cell lines), different from NK cells, NK-CTL failed to lyse autologous DC. However, after pulsing DC with a cytomegalovirus-derived, HLA-E-binding peptide recognized by NK-CTL, both iDC and mature DC became highly susceptible to lysis. On the other hand,the addition of the peptide resulted in the down-regulation of the NK-mediated lysis of the same autologous iDC. The capability of killing autologous DC, presenting a non-self, HLA-E-binding peptide, may represent a feedback mechanism by which NK-CTL down-regulate HLA-E-restricted responses to certain pathogens.