The transcription factor interferon regulatory factor 1 (IRF-1) is important during the maturation of natural killer 1.1+ T cell receptor-alpha/beta+ (NK1+ T) cells, natural killer cells, and intestinal intraepithelial T cells.
In contrast to conventional T cells, natural killer (NK) 1.1+ T cell receptor (TCR)-alpha/beta+ (NK1+T) cells, NK cells, and intestinal intraepithelial lymphocytes (IELs) bearing CD8-alpha/alpha chains constitutively express the interleukin (IL)-2 receptor (R)beta/15Rbeta chain. Recent studies have indicated that IL-2Rbeta/15Rbeta chain is required for the development of these lymphocyte subsets, outlining the importance of IL-15. In this study, we investigated the development of these lymphocyte subsets in interferon regulatory factor 1-deficient (IRF-1-/-) mice. Surprisingly, all of these lymphocyte subsets were severely reduced in IRF-1-/- mice. Within CD8-alpha/alpha+ intestinal IEL subset, TCR-gamma/delta+ cells and TCR-alpha/beta+ cells were equally affected by IRF gene disruption. In contrast to intestinal TCR-gamma/delta+ cells, thymic TCR-gamma/delta+ cells developed normally in IRF-1-/- mice. Northern blot analysis further revealed that the induction of IL-15 messenger RNA was impaired in IRF-1-/- bone marrow cells, and the recovery of these lymphocyte subsets was observed when IRF-1-/- cells were cultured with IL-15 in vitro. These data indicate that IRF-1 regulates IL-15 gene expression, which may control the development of NK1+T cells, NK cells, and CD8-alpha/alpha+ IELs.
Ohteki
T
T
Ontario Cancer Institute, Departments of Medical Biophysics and Immunology, Toronto, Ontario, Canada, M5G 2M9. tohteki@oci.utoronto.ca
Yoshida
H
H
Matsuyama
T
T
Duncan
G S
GS
Mak
T W
TW
Ohashi
P S
PS
D000818:Animals; D000941:Antigens / Q000032:analysis*; D000950:Antigens, Ly; D000954:Antigens, Surface; D004268:DNA-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation; D050856:Interferon Regulatory Factor-1; D019409:Interleukin-15 / Q000235:genetics; D007413:Intestinal Mucosa / Q000276:immunology*; D007694:Killer Cells, Natural / Q000502:physiology*; D037181:Lectins, C-Type; D051379:Mice; D008810:Mice, Inbred C57BL; D055651:NK Cell Lectin-Like Receptor Subfamily B; D010750:Phosphoproteins / Q000502:physiology*; D011506:Proteins / Q000032:analysis*; D012333:RNA, Messenger / Q000032:analysis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*
D000941:Antigens; D000950:Antigens, Ly; D000954:Antigens, Surface; D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; D019409:Interleukin-15; C494258:Irf1 protein, mouse; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D010750:Phosphoproteins; D011506:Proteins; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014157:Transcription Factors