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

Abstract

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 CD8α/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 CD8α/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.