Coyle A J, Le Gros G, Bertrand C, Tsuyuki S, Heusser C H, Kopf M, Anderson G P
Department of Asthma and Allergy, Ciba-Geigy Ltd., Basel, Switzerland.
Am J Respir Cell Mol Biol. 1995 Jul;13(1):54-9. doi: 10.1165/ajrcmb.13.1.7598937.
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 CD3/TCR 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 FACS-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.
用卵清蛋白致敏小鼠进行气溶胶抗原激发，可诱导嗜酸性气道炎症，该炎症依赖于白细胞介素（IL）-5和CD4⁺ 而非CD8⁺ T淋巴细胞。通过证明从致敏小鼠（而非对照小鼠）经荧光激活细胞分选术（FACS）分选纯化的肺T细胞在CD3/TCR复合物激活后产生IL-4、IL-5和IL-10，支持了CD4⁺ T细胞Th2表型的参与。为了确定IL-4在此过程中的作用，我们使用了通过同源重组缺失IL-4基因的小鼠。对IL-4基因靶向小鼠进行抗原激发导致嗜酸性炎症和IL-5分泌明显减轻。为了更全面地了解IL-4参与的时间，我们在抗原激发前或免疫期间给予中和性抗IL-4抗体（11B11）。在抗原激发前抑制IL-4对抗原诱导的嗜酸性粒细胞浸润影响不大。然而，当在免疫期间给予11B11时，嗜酸性粒细胞浸润明显减少。对经FACS分选的肺T细胞的CD3/TCR复合物进行交联显示，只有在免疫期间给予抗IL-4时，才会抑制T细胞衍生的IL-5和IgE产生。这些结果表明，IL-4对于局部Th2反应的诱导和肺部嗜酸性炎症的发展都至关重要。此外，我们提出IL-4和IL-5依次参与，IL-4使初始T细胞定向分化为Th2表型，该表型在气溶胶激发激活后分泌IL-5，导致嗜酸性粒细胞积聚。
