Hussell T, Baldwin C J, O'Garra A, Openshaw P J
National Heart and Lung Institute, Imperial College of Science, Technology and Medicine, St. Mary's Hospital, London, GB.
Eur J Immunol. 1997 Dec;27(12):3341-9. doi: 10.1002/eji.1830271233.
BALB/c mice vaccinated with vaccinia virus expressing the major surface glycoprotein G of respiratory syncytial virus (RSV) develop lung eosinophilia during RSV challenge. The G protein is remarkable in that it induces CD4+, but no CD8+ T cells in this mouse strain. Studies using passive T cell transfers show that co-injection of CD8+ T cells greatly reduces the Th2-driven lung eosinophilia caused by G-specific CD4+ T cells. By contrast, vaccination with the fusion protein (F) induces both CD8+ and CD4+ T cells, but not lung eosinophilia during RSV infection. These observations suggest that CD8+ T cells play a crucial role in preventing Th2-driven pathology. We therefore depleted mice with anti-CD8 antibodies in vivo. This treatment allowed lung eosinophilia to develop in F-primed mice. Depletion of interferon (IFN)-gamma had a similar effect, suggesting that secretion of this cytokine is the mechanism by which CD8+ T cells exert their effect. To test whether similar effects occurred in other strains of mice, RSV-infected C57BL/6 mice (which do not develop eosinophilia after sensitization to G) were treated with anti-IFN-gamma. Again, these mice developed eosinophilia. In this strain, genetic deletion of CD8-alpha, beta2-microglobulin or genes coding for the transporter associated with antigen presentation (which in each case eliminates CD8+ T cells) caused lung eosinophilia during RSV infection. These studies show the critical roles that CD8+ T cells and IFN-gamma production play in regulating Th2-driven eosinophilia and provide a unifying explanation for previous studies of lung eosinophilia. We propose that vaccines designed to enhance CD8+ T cell recognition might avoid disease caused by CD4+ Th2 cells.
用表达呼吸道合胞病毒（RSV）主要表面糖蛋白G的痘苗病毒接种的BALB/c小鼠在RSV攻击期间会出现肺部嗜酸性粒细胞增多。G蛋白的显著之处在于，它在该小鼠品系中诱导CD4+而非CD8+T细胞。使用被动T细胞转移的研究表明，共注射CD8+T细胞可大大减少由G特异性CD4+T细胞引起的Th2驱动的肺部嗜酸性粒细胞增多。相比之下，用融合蛋白（F）接种可诱导CD8+和CD4+T细胞，但在RSV感染期间不会引起肺部嗜酸性粒细胞增多。这些观察结果表明，CD8+T细胞在预防Th2驱动的病理过程中起关键作用。因此，我们在体内用抗CD8抗体使小鼠耗竭。这种处理使F预致敏小鼠出现肺部嗜酸性粒细胞增多。干扰素（IFN）-γ的耗竭也有类似效果，表明这种细胞因子的分泌是CD8+T细胞发挥作用的机制。为了测试在其他小鼠品系中是否会出现类似效果，用抗IFN-γ处理RSV感染的C57BL/6小鼠（对G致敏后不会出现嗜酸性粒细胞增多）。同样，这些小鼠出现了嗜酸性粒细胞增多。在该品系中，CD8-α、β2-微球蛋白或编码与抗原呈递相关转运体的基因的基因缺失（在每种情况下都会消除CD8+T细胞）在RSV感染期间导致肺部嗜酸性粒细胞增多。这些研究表明CD8+T细胞和IFN-γ产生在调节Th2驱动的嗜酸性粒细胞增多中所起的关键作用，并为先前关于肺部嗜酸性粒细胞增多的研究提供了统一的解释。我们提出，旨在增强CD8+T细胞识别的疫苗可能避免由CD4+Th2细胞引起的疾病。
