Developmental and functional defects of thymic and epidermal V gamma 3 cells in IL-15-deficient and IFN regulatory factor-1-deficient mice.
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.
De Creus
An
A
Department of Clinical Chemistry, Microbiology, and Immunology, University of Ghent, University Hospital, Ghent, Belgium.
Van Beneden
Katrien
K
Stevenaert
Frederik
F
Debacker
Veronique
V
Plum
Jean
J
Leclercq
Georges
G
D019264:Adoptive Transfer; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D046508:Culture Techniques; D003601:Cytotoxicity Tests, Immunologic; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology; D005333:Fetus; D050856:Interferon Regulatory Factor-1; D018664:Interleukin-12 / Q000494:pharmacology; D019409:Interleukin-15 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics* / Q000494:pharmacology; D007958:Leukocyte Count; D007970:Leukopenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis*; D012867:Skin / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000196:embryology / Q000276:immunology* / Q000637:transplantation
D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; D019409:Interleukin-15; C494258:Irf1 protein, mouse; D010750:Phosphoproteins; D012333:RNA, Messenger; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018664:Interleukin-12