The Transcription Factor Interferon Regulatory Factor 1 (IRF-1) Is Important during the Maturation of Natural Killer 1.1⁺ T Cell Receptor–α/β⁺ (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)-α/β⁺ (NK1⁺T) cells, NK cells, and intestinal intraepithelial lymphocytes (IELs) bearing CD8-α/α 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-α/α⁺ intestinal IEL subset, TCR-γ/δ⁺ cells and TCR-α/β⁺ cells were equally affected by IRF gene disruption. In contrast to intestinal TCR-γ/δ⁺ cells, thymic TCR-γ/δ⁺ 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-α/α⁺ IELs.