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-/⁺ (NK1⁺ T) Cells, Natural Killer Cells, and Intestinal Intraepithelial T Cells

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

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

In contrast to conventional T cells, natural killer (NK) 1.1⁺ T cell receptor (TCR)-/⁺ (NK1⁺T) cells, NK cells, and intestinal intraepithelial lymphocytes (IELs) bearing CD8-/ chains constitutively express the interleukin (IL)-2 receptor (R)/15R chain. Recent studies have indicated that IL-2R/15R 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-/⁺ intestinal IEL subset, TCR-/⁺ cells and TCR-/⁺ cells were equally affected by IRF gene disruption. In contrast to intestinal TCR-/⁺ cells, thymic TCR-/⁺ 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-/⁺ IELs.

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