Overexpression of interleukin-4 delays virus clearance in mice infected with respiratory syncytial virus
Overexpression of interleukin-4 delays virus clearance in mice infected with respiratory syncytial virus
复制标题
DOI：
10.1128/jvi.71.11.8672-8677.1997
复制
发表时间：
1997-11-01
影响因子：
5.4
通讯作者：
Graham, BS
中科院分区：
文献类型：
--
作者：
Fischer, JE;Johnson, JE;Graham, BS
虽然白细胞介素-4（IL-4）表达与疫苗增强的呼吸道合胞病毒（RSV）疾病有关，但其在介导对原发性RSV感染的免疫应答中的作用仍不清楚。为了评估IL-4产生对典型RSV感染的影响，用RSV鼻内攻击过表达或不能表达IL-4的转基因小鼠，并将它们的应答与亲本株的应答进行比较。IL-4缺陷小鼠从肺中清除病毒的速度与C57 BL/6对照小鼠一样快。相比之下，组成型过表达IL-4的小鼠与FVB/N对照株小鼠相比显示延迟的病毒清除，尽管峰值病毒滴度没有差异。IL-4过表达增加了随后的抗体应答的幅度。与对照组相比，从RSV攻击后IL-4过表达小鼠中收获的肺淋巴细胞显示RSV特异性细胞溶解活性降低。IL-4缺陷和IL-4过表达菌株均抵抗再攻击。这些数据意味着组成性IL-4表达延迟或抑制病毒特异性细胞毒性淋巴细胞群体的发展，这对清除原发性RSV感染很重要。
Although interleukin-4 (IL-4) expression has been implicated in vaccine-enhanced respiratory syncytial virus (RSV) disease, its role in mediating the immune response to primary RSV infection remains unclear. To assess the effect of IL-4 production on typical RSV infection, transgenic mice which either overexpress or fail to express IL-4 were challenged intranasally with RSV and their responses were compared to those of the parent strains. IL-4-deficient mice eliminated virus from the lung as quickly as did C57BL/6 controls. In contrast, mice which constitutively overexpress IL-4 showed delayed virus clearance compared with mice of the FVB/N control strain, although peak viral titers did not differ. IL-4 overexpression increased the magnitude of the subsequent antibody response. Lung lymphocytes harvested from IL-4-overexpressing mice post-RSV challenge showed diminished RSV-specific cytolytic activity compared with controls. Both IL-4-deficient and IL-4-overexpressing strains resisted rechallenge. These data imply that constitutive IL-4 expression delays or suppresses the development of a virus-specific cytotoxic lymphocyte population important in clearing primary RSV infection.