Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Scand J Immunol. 2012 Apr;75(4):409-18. doi: 10.1111/j.1365-3083.2012.02676.x.
Infections that occur early in life may have a beneficial effect on the immune system and thereby reduce the risk of allergen sensitization and/or allergic disease. It is not yet clear to what extent specific virus and/or bacteria can mediate this effect. The purpose of this study was to assess the role of virus and bacteria in CD4(+) T cell-derived cytokine production in newborns. We compared the effects of five bacteria (Staphlococcus aureus, Escherichia coli, Clostridium difficile, Lactobacillus rhamnosus and Bifidobacterium bifidus) and seven virus (adenovirus, coronavirus, cytomegalovirus, herpes simplex virus, influenza virus, morbillivirus and poliovirus) on the Th1/Th2 cytokine production in mixed lymphocyte reactions using CD4(+) T cells from cord blood cocultured with allogenic myeloid or plasmacytoid dendritic cells. When comparing the baseline cytokine production prior to microbial stimulation, we observed that cord plasmacytoid DC were stronger inducers of Th2 cytokines (IL-5 and IL-13) compared with cord myeloid DC and to adult DC. When adding microbes to these cultures, bacteria and virus differed in two major respects; Firstly, all enveloped viruses, but none of the bacteria, blocked Th2 (IL-13) production by cord CD4(+) cells. Secondly, all Gram-positive bacteria, but none of the virus, induced IL-12p40 responses, but the IL-12p40 responses did not affect Th1 cytokine production (IFN-γ). Instead, Th1 responses were correlated with the capacity to induce IFN-α secretion, which in cord cells were induced by S. aureus and influenza virus alone. These data imply that enveloped virus can deviate Th2 responses in human cord T cells.
生命早期发生的感染可能对免疫系统产生有益影响,从而降低变应原致敏和/或过敏性疾病的风险。目前尚不清楚特定的病毒和/或细菌在多大程度上可以介导这种效应。本研究旨在评估病毒和细菌在新生儿 CD4+T 细胞来源的细胞因子产生中的作用。我们比较了五种细菌(金黄色葡萄球菌、大肠杆菌、艰难梭菌、鼠李糖乳杆菌和双歧杆菌)和七种病毒(腺病毒、冠状病毒、巨细胞病毒、单纯疱疹病毒、流感病毒、麻疹病毒和脊髓灰质炎病毒)对混合淋巴细胞反应中 CD4+T 细胞产生 Th1/Th2 细胞因子的影响,方法是将脐带血 CD4+T 细胞与同种异体髓样或浆细胞样树突状细胞共培养。在比较微生物刺激前的基础细胞因子产生时,我们观察到脐带浆细胞样 DC 比脐带髓样 DC 和成人 DC 更能诱导 Th2 细胞因子(IL-5 和 IL-13)的产生。当将微生物加入这些培养物中时,细菌和病毒在两个主要方面有所不同;首先,所有包膜病毒,但没有一种细菌,阻断了脐带 CD4+细胞产生 Th2(IL-13)。其次,所有革兰氏阳性菌,但没有一种病毒,诱导了 IL-12p40 反应,但 IL-12p40 反应不会影响 Th1 细胞因子的产生(IFN-γ)。相反,Th1 反应与诱导 IFN-α分泌的能力相关,而在脐带细胞中,S. aureus 和流感病毒单独诱导了 IFN-α的分泌。这些数据表明,包膜病毒可以使人类脐带 T 细胞的 Th2 反应发生偏离。