In this study, the role of IL-15 and its regulation by the transcription factor IFN regulatory factor-1 (IRF-1) in murine V gamma 3 T cell development and activity is assessed. Compared with wild-type (WT) mice, reduced numbers of mature V gamma 3 cells were found in the fetal thymus of IL-15(-/-) mice, while IRF-1(-/-) mice displayed normal frequencies. V gamma 3(+) dendritic epidermal T cells (DETCs) were absent in IL-15(-/-) mice but present in IRF-1(-/-) mice. DETCs from IRF-1(-/-) mice displayed morphologically a less mature phenotype and showed different emergence kinetics during ontogeny. This corresponded with lower IL-15 mRNA levels in the skin epidermis. Comparable levels of IL-7 were found in the skin of WT and IL-15(-/-) mice. Adoptive transfer experiments of WT fetal thymocytes into IL-15(-/-) mice did not result in the development of V gamma 3(+) DETCs, confirming the nonredundant role of IL-15 in the skin during DETC development. In vitro, cytolytic activity of IL-15(-/-) V gamma 3 cells was normal after stimulation with IL-15 and was further enhanced by addition of IL-12. In contrast, cytolytic activity of IRF-1(-/-) V gamma 3 cells remained defective after stimulation with IL-15 in combination with IL-12. These data suggest that IL-15 is redundant for the development and/or survival of mature V gamma 3 cells in the fetal thymus, whereas it is essential for the localization of V gamma 3 cells in the skin. Furthermore, a possible role for IRF-1 in inducing morphological maturation of DETCs and cytolytic capacity of V gamma 3 cells is suggested.