Hodge M R, Ranger A M, Charles de la Brousse F, Hoey T, Grusby M J, Glimcher L H
Department of Cancer Biology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Immunity. 1996 Apr;4(4):397-405. doi: 10.1016/s1074-7613(00)80253-8.
NF-ATp is a member of a family of genes that encodes the cytoplasmic component of the nuclear factor of activated T cells (NF-AT). In this study, we show that mice with a null mutation in the NF-ATp gene have splenomegaly with hyperproliferation of both B and T cells. They also display early defects in the transcription of multiple genes encoding cytokines and cell surface receptors, including CD40L and FasL. A striking defect in early IL-4 production was observed after ligation of the TCR complex by treatment with anti-CD3 in vivo. The transcription of other cytokines including IL-13, GM-CSF, and TNF alpha was also affected, though to a lesser degree. Interestingly, the cytokines IL-2 and IFN gamma were minimally affected. Despite this early defect in IL-4 transcription, Th2 development was actually enhanced at later timepoints as evidenced by increased IL-4 production and IgE levels in situations that favor the formation of Th2 cells both in vitro and in vivo. These data suggest that NF-ATp may be involved in cell growth, and that it is important for the balanced transcription of the IL-4 gene during the course of an immune response.
NF-ATp是一个基因家族的成员，该家族编码活化T细胞核因子（NF-AT）的细胞质成分。在本研究中，我们发现NF-ATp基因发生无效突变的小鼠出现脾肿大，同时B细胞和T细胞均过度增殖。它们还在多个编码细胞因子和细胞表面受体（包括CD40L和FasL）的基因转录方面表现出早期缺陷。在用抗CD3体内处理使TCR复合物连接后，观察到早期IL-4产生存在显著缺陷。包括IL-13、GM-CSF和TNFα在内的其他细胞因子的转录也受到影响，不过程度较轻。有趣的是细胞因子IL-2和IFNγ受影响最小。尽管IL-4转录存在这种早期缺陷，但在体外和体内有利于Th2细胞形成的情况下，后期IL-4产生增加和IgE水平升高证明Th2发育实际上得到增强。这些数据表明NF-ATp可能参与细胞生长，并且在免疫反应过程中对IL-4基因的平衡转录很重要。
