Jarvis J N, Zhao L, Xu C S, Moore H T, Berry S
Division of Immunology/Rheumatology, Wayne State University School of Medicine, Detroit, Mich., USA.
Biol Neonate. 1997;72(6):329-36. doi: 10.1159/000244502.
Fetal and neonatal lymphocytes are relatively resistant to activation and cytokine production when stimulated either via their T-cell antigen receptors or lectins. The molecular mechanism(s) responsible for this phenomenon have not been clearly elucidated. We have hypothesized that such defects in fetal/neonatal T-cell activation may be due to lack of expression of the transcriptional regulatory elements required for T-cell activation. We used reverse transcriptase-polymerase chain reaction to examine both fetal and term neonatal cord bloods for mRNA expression of three transcription factors implicated in T-cell activation: c-jun, c-fos, and NF kappa B (p50 subunit). We demonstrate that mRNAs for all three of these regulatory factors are expressed in fetal blood cells by the 27th week of gestation and in term cord bloods. Activation of term infant cord blood mononuclear cells with anti-CD3 monoclonal antibodies resulted in up-regulation of both c-jun and c-fos mRNAs within 15 min of stimulation. However, secretion of IL-2 by anti-CD3-stimulated cord blood mononuclear cells was still blunted compared with control cells from adults. We conclude that fetal nucleated blood cells constitutively express important genes for cytokine regulation and are able to increase intracellular accumulation of the mRNAs for these factors in response to anti-CD3 stimulation. Thus, qualitative differences in the capacity to regulate these factors could not be shown in fetal blood cells. Quantitative experiments comparing binding of these transcription factors to the IL-2 promoter are currently under investigation.
胎儿和新生儿的淋巴细胞在通过其T细胞抗原受体或凝集素刺激时,对激活和细胞因子产生具有相对抗性。导致这种现象的分子机制尚未完全阐明。我们推测,胎儿/新生儿T细胞激活中的此类缺陷可能是由于缺乏T细胞激活所需的转录调节元件的表达。我们使用逆转录聚合酶链反应来检测胎儿和足月新生儿脐带血中与T细胞激活相关的三种转录因子:c-jun、c-fos和NF-κB(p50亚基)的mRNA表达。我们证明,在妊娠第27周时,胎儿血细胞以及足月脐带血中均表达这三种调节因子的mRNA。用抗CD3单克隆抗体激活足月婴儿脐带血单个核细胞会导致在刺激后15分钟内c-jun和c-fos mRNA上调。然而,与来自成人的对照细胞相比,抗CD3刺激的脐带血单个核细胞分泌IL-2的能力仍然较弱。我们得出结论,胎儿有核血细胞组成性表达细胞因子调节所需的重要基因,并能够在抗CD3刺激下增加这些因子的mRNA在细胞内的积累。因此,在胎儿血细胞中未发现调节这些因子能力的定性差异。目前正在进行比较这些转录因子与IL-2启动子结合的定量实验研究。