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3 Cells in IL-15-Deficient and IFN Regulatory Factor-1-Deficient Mice1
Department of Clinical Chemistry, Microbiology, and Immunology, University of Ghent, University Hospital, Ghent, Belgium
In this study, the role of IL-15 and its regulation by the
transcription factor IFN regulatory factor-1 (IRF-1) in murine V
3 T
cell development and activity is assessed. Compared with wild-type (WT)
mice, reduced numbers of mature V3 cells were found in the fetal
thymus of IL-15-/- mice, while IRF-1-/-
mice displayed normal frequencies. V3+ 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 V3+ DETCs, confirming the nonredundant
role of IL-15 in the skin during DETC development. In vitro, cytolytic
activity of IL-15-/- V3 cells was normal after
stimulation with IL-15 and was further enhanced by addition of IL-12.
In contrast, cytolytic activity of IRF-1-/- V3 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 V3 cells in the fetal thymus, whereas it
is essential for the localization of V3 cells in the skin.
Furthermore, a possible role for IRF-1 in inducing morphological
maturation of DETCs and cytolytic capacity of V3 cells is
suggested.
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