CD8+ T cells control Th2-driven pathology during pulmonary respiratory syncytial virus infection
CD8+ T cells control Th2-driven pathology during pulmonary respiratory syncytial virus infection
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DOI：
10.1002/eji.1830271233
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发表时间：
1997-12-01
影响因子：
5.4
通讯作者：
Openshaw, PJM
中科院分区：
文献类型：
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作者：
Hussell, T;Baldwin, CJ;Openshaw, PJM
用表达呼吸道合胞病毒（RSV）主要表面糖蛋白G的牛痘病毒接种的BALB/c小鼠在RSV攻击期间发生肺嗜酸性粒细胞增多症。G蛋白的显著之处在于，它在这种小鼠品系中诱导CD 4（+）T细胞，但不诱导CD 8（+）T细胞。使用被动T细胞转移的研究表明，共注射CD 8（+）T细胞大大减少了由G特异性CD 4（+）T细胞引起的Th 2驱动的肺嗜酸性粒细胞增多症。相比之下，用融合蛋白（F）接种诱导了CD 8（+）和CD 4（+）T细胞，但在RSV感染期间不诱导肺嗜酸性粒细胞增多。这些观察结果表明，CD 8（+）T细胞在预防Th 2驱动的病理中起着至关重要的作用。因此，我们在体内用抗CD 8抗体耗尽小鼠。该处理允许肺嗜酸性粒细胞增多症在F致敏小鼠中发展。干扰素（IFN）-γ的耗竭也有类似的效果，表明这种细胞因子的分泌是CD 8（+）T细胞发挥作用的机制。为了测试在其他品系的小鼠中是否发生类似的作用，用抗IFN-γ治疗RSV感染的C57 BL/6小鼠（其在对G致敏后不发生嗜酸性粒细胞增多症）。这些小鼠再次出现嗜酸性粒细胞增多。在该毒株中，在RSV感染期间，CD 8-α、β 2-微球蛋白或编码与抗原呈递相关的转运蛋白（在每种情况下消除CD 8（+）T细胞）的基因缺失导致肺嗜酸性粒细胞增多症。这些研究表明，CD 8（+）T细胞和IFN-γ的产生在调节Th 2驱动的嗜酸性粒细胞增多中起着关键作用，并为以前的肺嗜酸性粒细胞增多研究提供了统一的解释。我们认为，设计用于增强CD 8（+）T细胞识别的疫苗可能会避免由CD 4（+）Th 2细胞引起的疾病。
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, beta 2-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.