The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/3/967/ $5.00
The Journal of Experimental Medicine, Volume 187, Number 6, March 16, 1998 967-972


Brief Definitive Reports

The Transcription Factor Interferon Regulatory Factor 1 (IRF-1) Is Important during the Maturation of Natural Killer 1.1+ T Cell Receptor–{alpha}+ (NK1+ T) Cells, Natural Killer Cells, and Intestinal Intraepithelial T Cells

Toshiaki Ohteki*, Hiroki Yoshida{ddagger}, Toshifumi Matsuyama{ddagger}, Gordon S. Duncan{ddagger}, Tak W. Mak*,{ddagger}, and Pamela S. Ohashi*

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

In contrast to conventional T cells, natural killer (NK) 1.1+ T cell receptor (TCR)-{alpha}+ (NK1+T) cells, NK cells, and intestinal intraepithelial lymphocytes (IELs) bearing CD8-{alpha}/{alpha} chains constitutively express the interleukin (IL)-2 receptor (R)β/15Rβ chain. Recent studies have indicated that IL-2Rβ/15Rβ 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}+ 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.


Address correspondence to Toshiaki Ohteki, Ontario Cancer Institute, Departments of Medical Biophysics and Immunology, 610 University Ave., Toronto, Ontario, Canada, M5G 2M9. Phone: 416-946-2000; Fax: 416-946-2086; E-mail: tohteki{at}oci.utoronto.ca


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