Alwan W H, Kozlowska W J, Openshaw P J
Department of Medicine, Imperial College of Science, Technology and Medicine, London, UK.
J Exp Med. 1994 Jan 1;179(1):81-9. doi: 10.1084/jem.179.1.81.
T cells appear to play a central role in viral bronchiolitis, but the effects of different functional and phenotypic subgroups of T cells have not been defined. To test the activities of T cells recognizing individual proteins of respiratory syncytial (RS) virus, virus-specific T cell lines were produced from mice primed by scarification with recombinant vaccinia viruses expressing the major surface glycoprotein (G), fusion protein (F) or second matrix (22K) protein of RS virus. As previously reported, the in vitro characteristics of these cells are predetermined by the choice of RS virus protein: 22K-specific cells are predominantly class I-restricted cytolytic CD8+ cells; F-specific cells, a mixture of cytolytic CD8+ cells and CD4+ cells with a T helper 1 cell (Th1) cytokine secretion profile, whereas those from G-sensitized mice are almost exclusively CD4+, with Th2 characteristics. Mice infected intranasally with RS virus showed mild illness and recovered fully, but developed respiratory distress after intravenous injections of T cells. Dose-for-dose, infected mice receiving G-specific cells suffered the most severe (sometimes fatal) illness, characterized by lung hemorrhage, pulmonary neutrophil recruitment (shock lung) and intense pulmonary eosinophilia. This disease was further enhanced by coinjection of 22K-specific cells, which alone caused mild shock lung without eosinophilia. F-specific cells caused minimal enhancement of pathology and had little or no effect on the disease caused by G-specific cells. Each cell line reduced lung virus titer and combined injections of G- and 22K-specific cells eliminated infection completely. The in vitro characteristics of these antiviral T cell lines therefore predict the pathological effects in vivo. Moreover, different forms of viral bronchiolitis can be caused by functionally distinct types of activated T cell.
T细胞似乎在病毒性细支气管炎中发挥核心作用，但T细胞不同功能和表型亚群的作用尚未明确。为了检测识别呼吸道合胞（RS）病毒单个蛋白的T细胞活性，用表达RS病毒主要表面糖蛋白（G）、融合蛋白（F）或第二基质（22K）蛋白的重组痘苗病毒划痕免疫小鼠，从这些小鼠中制备病毒特异性T细胞系。如先前报道，这些细胞的体外特性由所选择的RS病毒蛋白预先决定：22K特异性细胞主要是I类限制性细胞毒性CD8+细胞；F特异性细胞是细胞毒性CD8+细胞和具有T辅助1细胞（Th1）细胞因子分泌谱的CD4+细胞的混合物，而来自G致敏小鼠的细胞几乎全是具有Th2特征的CD4+细胞。经鼻感染RS病毒的小鼠表现出轻度疾病并完全康复，但静脉注射T细胞后出现呼吸窘迫。在相同剂量下，接受G特异性细胞的感染小鼠患病最严重（有时致命），其特征为肺出血、肺中性粒细胞募集（休克肺）和强烈的肺嗜酸性粒细胞增多。同时注射22K特异性细胞会进一步加重这种疾病，单独注射22K特异性细胞只会引起轻度无嗜酸性粒细胞的休克肺。F特异性细胞导致的病理增强最小，对G特异性细胞引起的疾病几乎没有影响。每个细胞系都降低了肺病毒滴度，联合注射G特异性细胞和22K特异性细胞可完全消除感染。因此，这些抗病毒T细胞系的体外特性可预测其体内的病理效应。此外，不同形式的病毒性细支气管炎可由功能不同类型的活化T细胞引起。
