Kauth Marion, Grage-Griebenow Evelin, Rohde Gernot, Anhenn Olaf, Wiethege Almut, Schultze-Werninghaus Gerhard, Bufe Albrecht
Department of Experimental Pneumology, Ruhr University Bochum, Bochum, Germany.
Int Arch Allergy Immunol. 2007;142(2):116-26. doi: 10.1159/000096381. Epub 2006 Oct 18.
Respiratory syncytial virus (RSV) is known as a causal factor of severe bronchiolitis in young children. It has also been detected in patients with chronic obstructive pulmonary disease (COPD), a disease that is associated with an increased number of T cells in the bronchial mucosa. Here, we investigated the potential direct interaction between RSV and T cells and its impact on cytokine response.
Purified human peripheral blood T cells were stimulated with RSV in vitro and analyzed by flow cytometry and fluorescence microscopy. Cytokine expression and release were measured in T cell cultures and in cocultures with peripheral blood monocytes as well as with alveolar macrophages from bronchoalveolar lavage fluid by quantitative real-time PCR and ELISA.
It was shown that RSV adhered to the surface of T cells. Stimulation of purified T cells with RSV led to a significant increase in interleukin (IL)-10 mRNA expression after 24 h. Moreover, in cocultures of T cells with monocytes or alveolar macrophages, IL-10 production was synergistically upregulated 24 h after stimulation with RSV.
These results suggest that RSV can cause an excessive IL-10 response leading to downregulation of antiviral defense mechanisms and reduced elimination of respiratory pathogens when antigen-presenting cells and T cells are simultaneously present on the site of infection. This effect may possibly contribute to high frequencies of respiratory pathogens found in patients with chronic inflammatory airway diseases associated with increased local T cell influx such as COPD.
呼吸道合胞病毒（RSV）是幼儿严重细支气管炎的致病因素。在慢性阻塞性肺疾病（COPD）患者中也检测到该病毒，COPD与支气管黏膜中T细胞数量增加有关。在此，我们研究了RSV与T细胞之间潜在的直接相互作用及其对细胞因子反应的影响。
用RSV体外刺激纯化的人外周血T细胞，并通过流式细胞术和荧光显微镜进行分析。通过定量实时PCR和酶联免疫吸附测定法，在T细胞培养物以及与外周血单核细胞和支气管肺泡灌洗液体外肺泡巨噬细胞的共培养物中测量细胞因子的表达和释放。
结果显示RSV附着于T细胞表面。用RSV刺激纯化的T细胞24小时后，白细胞介素（IL）-10 mRNA表达显著增加。此外，在T细胞与单核细胞或肺泡巨噬细胞的共培养物中，用RSV刺激24小时后，IL-10的产生协同上调。
这些结果表明，当抗原呈递细胞和T细胞同时存在于感染部位时，RSV可导致IL-10反应过度，从而导致抗病毒防御机制下调以及呼吸道病原体清除减少。这种效应可能导致在与局部T细胞流入增加相关的慢性炎症性气道疾病患者（如COPD）中发现呼吸道病原体的频率较高。
