DISTINCT TYPES OF LUNG-DISEASE CAUSED BY FUNCTIONAL SUBSETS OF ANTIVIRAL T-CELLS
DISTINCT TYPES OF LUNG-DISEASE CAUSED BY FUNCTIONAL SUBSETS OF ANTIVIRAL T-CELLS
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DOI：
10.1084/jem.179.1.81
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发表时间：
1994-01-01
影响因子：
15.3
通讯作者：
OPENSHAW, PJM
中科院分区：
文献类型：
--
作者：
ALWAN, WH;KOZLOWSKA, WJ;OPENSHAW, PJM
T细胞似乎在病毒性细支气管炎中发挥核心作用，但T细胞的不同功能和表型亚群的作用尚未确定。为了检测T细胞识别呼吸道合胞病毒（RS）的单个蛋白的活性，从通过划痕用表达RS病毒的主要表面糖蛋白（G）、融合蛋白（F）或第二基质（22 K）蛋白的重组牛痘病毒致敏的小鼠产生病毒特异性T细胞系。如先前所报道的，这些细胞的体外特征通过RS病毒蛋白的选择而预先确定：22 K特异性细胞主要是I类限制性溶细胞性CD 8（+）细胞; F-特异性细胞，即溶细胞性CD 8（+）细胞和CD 4（+）细胞的混合物，具有辅助性T细胞1（Th 1）细胞因子分泌特征，而来自G-致敏小鼠的细胞几乎全部是CD 4（+），Th 2的特征。鼻内感染RS病毒的小鼠表现出轻微的疾病并完全康复，但在静脉注射T细胞后出现呼吸窘迫。接受G特异性细胞的剂量-剂量感染小鼠发生最严重（有时致命）的疾病，特征为肺出血、肺中性粒细胞募集（休克肺）和严重的肺嗜酸性粒细胞增多。共注射22 K特异性细胞进一步增强了这种疾病，单独注射22 K特异性细胞可引起轻度休克肺，但无嗜酸性粒细胞增多。F特异性细胞引起的病理学增强最小，对G特异性细胞引起的疾病几乎没有影响。每种细胞系都降低了肺病毒滴度，G和22 K特异性细胞的联合注射完全消除了感染。因此，这些抗病毒T细胞系的体外特征预测了体内的病理效应。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。
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.