INTERLEUKIN-4 IS REQUIRED FOR THE INDUCTION OF LUNG TH2 MUCOSAL IMMUNITY
INTERLEUKIN-4 IS REQUIRED FOR THE INDUCTION OF LUNG TH2 MUCOSAL IMMUNITY
复制标题
DOI：
10.1165/ajrcmb.13.1.7598937
复制
发表时间：
1995-07-01
影响因子：
6.4
通讯作者：
ANDERSON, GP
中科院分区：
文献类型：
--
作者：
COYLE, AJ;LEGROS, G;ANDERSON, GP
卵清蛋白致敏小鼠的气溶胶抗原激发诱导嗜酸性粒细胞气道炎症，该炎症依赖于白细胞介素（IL）-5和CD 4（+）T淋巴细胞，而不是CD 8（+）T淋巴细胞。CD 4（+）T细胞的Th 2表型的参与通过证明来自致敏而非对照小鼠的经FACS分选的纯化肺T细胞在GD 3/TGR复合物活化后产生IL-4、IL-5和IL-10而得到支持。为了确定IL-4在这一过程中的作用，我们使用了通过同源重组删除IL-4基因的小鼠。IL-4基因靶向小鼠的抗原攻击导致嗜酸性粒细胞炎症和IL-5分泌的显著减弱。为了更全面地了解IL-4参与的时间，我们在抗原攻击前或免疫期间立即施用中和抗IL-4抗体（11B 11）。在抗原激发前抑制IL-4对抗原诱导的嗜酸性粒细胞浸润几乎没有影响。然而，当在免疫期间施用11B 11时，嗜酸性粒细胞浸润显著减少。经FAGS分选的肺T细胞的CD 3/TCR复合物的交联揭示，仅当在免疫期间施用抗IL-4时，才存在T细胞衍生的IL-5和IgE产生的抑制。这些结果表明，IL-4是中央的诱导局部Th 2反应和嗜酸性粒细胞炎症的肺的发展。此外，我们提出了IL-4和IL-5的顺序参与，IL-4将幼稚T细胞转化为Th 2表型，其在通过气溶胶激发激活后分泌IL-5，导致嗜酸性粒细胞积累。
Aerosol antigen challenge of ovalbumin-sensitized mice induced an eosinophilic airway inflammation that was dependent on interleukin (IL)-5 and CD4(+), but not CD8(+), T lymphocytes. The involvement of the Th2 phenotype of CD4(+) T cells was supported by demonstrating that FACS-sorted purified lung T cells from sensitized, but not control, mice produced IL-4, IL-5, and IL-10 after activation of the GD3/TGR complex. To determine the role of IL-4 in this process, we used mice in which the gene for IL-4 was deleted by homologous recombination. Antigen challenge of IL-4 gene-targeted mice resulted in a marked attenuation of eosinophilic inflammation and IL-5 secretion. To more fully understand the time when IL-4 was involved, we administered a neutralizing anti-IL-4 antibody (11B11) either immediately before antigen challenge or during immunization. Inhibition of IL-4 before antigen challenge had little effect on antigen-induced eosinophil infiltration. However, when 11B11 was administered during immunization, there was a marked reduction in eosinophil infiltration. Cross-linking of the CD3/TCR complex of FAGS-sorted lung T cells revealed that only when anti-IL-4 was administered during immunization was there an inhibition of T cell-derived IL-5 and IgE production. These results suggest that IL-4 is central both to the induction of a local Th2 response and to the development of eosinophilic inflammation of the lung. Moreover, we suggest a sequential involvement of IL-4 and IL-5, with IL-4 committing naive T cells to a Th2 phenotype which upon activation by aerosol provocation secrete IL-5, resulting in eosinophil accumulation.