Townsend Michael J, Weinmann Amy S, Matsuda Jennifer L, Salomon Rachelle, Farnham Peggy J, Biron Christine A, Gapin Laurent, Glimcher Laurie H
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Harvard Medical School, Boston, MA 02115, USA.
Immunity. 2004 Apr;20(4):477-94. doi: 10.1016/s1074-7613(04)00076-7.
Natural killer (NK) and CD1d-restricted Valpha14i natural killer T (NKT) cells play a critical early role in host defense. Here we show that mice with a targeted deletion of T-bet, a T-box transcription factor required for Th1 cell differentiation, have a profound, stem cell-intrinsic defect in their ability to generate mature NK and Valpha14i NKT cells. Both cell types fail to complete normal terminal maturation and are present in decreased numbers in peripheral lymphoid organs of T-bet(-/-) mice. T-bet expression is regulated during NK cell differentiation by NK-activating receptors and cytokines known to control NK development and effector function. Our results identify T-bet as a key factor in the terminal maturation and peripheral homeostasis of NK and Valpha14i NKT cells.
自然杀伤（NK）细胞和CD1d限制性Vα14i自然杀伤T（NKT）细胞在宿主防御中发挥关键的早期作用。在此，我们表明，T-bet（一种Th1细胞分化所需的T-box转录因子）基因靶向缺失的小鼠，在生成成熟NK细胞和Vα14i NKT细胞的能力方面存在严重的、干细胞内在缺陷。这两种细胞类型均无法完成正常的终末成熟，且在T-bet（-/-）小鼠的外周淋巴器官中数量减少。在NK细胞分化过程中，T-bet的表达受已知控制NK细胞发育和效应功能的NK激活受体和细胞因子调节。我们的结果表明，T-bet是NK细胞和Vα14i NKT细胞终末成熟及外周稳态的关键因子。
