Yu Hong-Ren, Chang Jen-Chieh, Chen Rong-Fu, Chuang Hau, Hong Kuo-Ching, Wang Lin, Yang Kuender D
Division of Clinical Immunology & Allergy, Chang Gung Children's Hospital, Chang Gung University, Kaohsiung, Taiwan, ROC.
J Leukoc Biol. 2003 Nov;74(5):952-8. doi: 10.1189/jlb.0902474. Epub 2003 Jul 22.
Neonates are known to have poor cellular immunity, especially poor Th1 response. We investigated how neonatal mononuclear cells raised different Th1/Th2 reactions in response to different antigens. Employing Dermatophagoides pteronyssinus (Der p) extract and varicella zoster virus (VZV) as antigens, we assessed Th1/Th2 reactions as demonstrated by IL-4/IFNgamma production and mRNA expression, and transcriptional factors T-bet/GATA-3 mRNA expression in mononuclear cells from human umbilical cord blood (CBMC). Results showed that VZV induced a dramatic increase of IFNgamma production by adult peripheral blood mononuclear cells (PBMC), whereas VZV did not drive CBMC to release significant IFNgamma production (1614.7+/-362.0 vs. 49.0+/-29.3,p<0.005). However, Der p induced higher IFNgamma production by CBMC than VZV (298.1+/-171.8 vs. 49.0+/-29.3, P=0.047). In contrast, VZV did not induce significant IL-4 production either by CBMC or by PBMC. Der p induced a comparative IL-4 production by CBMC and PBMC (2.58+/-0.84 vs. 2.04+/-0.37, p>0.05). A real-time RT-PCR analysis of IL-4 and IFNgamma mRNA expression showed that VZV induced a significantly higher IFNgamma, but not IL-4, mRNA expression in PBMC than CBMC. Der p did not induce significant difference of IFNgamma or IL-4 mRNA expression in PBMC and CBMC. VZV enhanced Th1-related transcription factor T-bet mRNA expression, in association with later down-regulation of Th2-related GATA-3 mRNA expression in PBMC. However, VZV did not up-regulate T-bet or down-regulate GATA-3 expression significantly in CBMC. In contrast, Der p induced an early GATA-3 expression and later T-bet expression in CBMC. These results suggest that different antigens trigger various Th1/Th2 reactions in PBMC and CBMC resulting from kinetic changes of T-bet/GATA-3 expression.
众所周知，新生儿的细胞免疫功能较差，尤其是Th1反应较弱。我们研究了新生儿单核细胞如何针对不同抗原引发不同的Th1/Th2反应。我们以户尘螨提取物（Der p）和水痘带状疱疹病毒（VZV）作为抗原，通过检测IL-4/IFNγ的产生及mRNA表达，以及转录因子T-bet/GATA-3 mRNA在人脐带血单个核细胞（CBMC）中的表达，来评估Th1/Th2反应。结果显示，VZV可使成人外周血单个核细胞（PBMC）的IFNγ产生显著增加，而VZV并不能促使CBMC释放大量的IFNγ（1614.7±362.0 vs. 49.0±29.3，p<0.005）。然而，Der p诱导CBMC产生的IFNγ高于VZV（298.1±171.8 vs. 49.0±29.3，P = 0.047）。相反，VZV无论是对CBMC还是PBMC，均未诱导出显著的IL-4产生。Der p诱导CBMC和PBMC产生的IL-4相当（2.58±0.84 vs. 2.04±0.37，p>0.05）。对IL-4和IFNγ mRNA表达进行实时RT-PCR分析显示，VZV诱导PBMC中IFNγ mRNA的表达显著高于CBMC，但对IL-4 mRNA的表达无此作用。Der p对PBMC和CBMC中IFNγ或IL-4 mRNA的表达未诱导出显著差异。VZV可增强PBMC中Th1相关转录因子T-bet mRNA的表达，并伴随Th2相关的GATA-3 mRNA表达随后下调。然而，VZV对CBMC中T-bet的上调或GATA-3的下调作用均不显著。相反，Der p在CBMC中诱导早期GATA-3表达及随后的T-bet表达。这些结果表明，不同抗原通过T-bet/GATA-3表达的动力学变化，在PBMC和CBMC中引发了不同的Th1/Th2反应。
