The Journal of Experimental Medicine
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J. Exp. Med., Volume 187, Number 6, March 16, 1998 967-972

BRIEF DEFINITIVE REPORT:
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

By Toshiaki Ohteki,* Hiroki Yoshida,Dagger Toshifumi Matsuyama,Dagger Gordon S. Duncan,Dagger Tak W. Mak,*Dagger and Pamela S. Ohashi*

From the * Ontario Cancer Institute, Departments of Medical Biophysics and Immunology, Toronto, Ontario, Canada, M5G 2M9; and the Dagger  Amgen Institute, Toronto, Ontario, Canada, M5G 2C1

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.


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