Walunas T L, Wang B, Wang C R, Leiden J M
Department of Medicine and Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL 60637, USA.
J Immunol. 2000 Mar 15;164(6):2857-60. doi: 10.4049/jimmunol.164.6.2857.
Ets1-deficient mice develop B and T cells but display a severe defect in the development of the NK cell lineage. In this report, we demonstrate that Ets1 is also required for the development of NK1.1+ T (NK T) cells. We observed significantly decreased numbers of NK T cells in the thymus, spleen, and liver of Ets1-deficient mice. These organs also contained markedly decreased levels of the canonical Valpha14-Jalpha281 TCRalpha transcript seen in NK T cells. Unlike wild-type NK T cells, Ets1-deficient thymocytes failed to produce detectable levels of IL-4 following anti-CD3 stimulation. The absence of NK T cells in the Ets1-deficient mice was not associated with defective expression of CD1, an MHC class I molecule required for NK T cell development. We conclude that Ets1 defines a novel transcriptional regulatory pathway that is required for the development of both the NK and NK T cell lineages.
Ets1基因缺陷型小鼠能够发育出B细胞和T细胞,但在自然杀伤(NK)细胞系的发育过程中表现出严重缺陷。在本报告中,我们证明Ets1对于NK1.1 + T(NKT)细胞的发育也是必需的。我们观察到Ets1基因缺陷型小鼠的胸腺、脾脏和肝脏中NKT细胞数量显著减少。这些器官中NKT细胞中可见的典型Vα14-Jα281 TCRα转录本水平也明显降低。与野生型NKT细胞不同,Ets1基因缺陷型胸腺细胞在抗CD3刺激后无法产生可检测水平的白细胞介素-4。Ets1基因缺陷型小鼠中NKT细胞的缺失与CD1的表达缺陷无关,CD1是NKT细胞发育所需的一种MHC I类分子。我们得出结论,Ets1定义了一条新的转录调控途径,该途径对于NK和NKT细胞系的发育都是必需的。