期刊
JOURNAL OF LEUKOCYTE BIOLOGY
卷 93, 期 6, 页码 933-942出版社
OXFORD UNIV PRESS
DOI: 10.1189/jlb.1012498
关键词
viral infection; infants; T helper cells
资金
- U.S. National Institutes of Health [R01AI090059, R01ES015050, P42ES013648]
RSV is the major cause of severe bronchiolitis in infants, and severe bronchiolitis as a result of RSV is associated with subsequent asthma development. A biased Th2 immune response is thought to be responsible for neonatal RSV pathogenesis; however, molecular mechanisms remain elusive. Our data demonstrate, for the first time, that IL-4R alpha is up-regulated in vitro on human CD4(+) T cells from cord blood following RSV stimulation and in vivo on mouse pulmonary CD4(+) T cells upon reinfection of mice, initially infected as neonates. Th cell-specific deletion of II4ra attenuated Th2 responses and abolished the immunopathophysiology upon reinfection, including airway hyper-reactivity, eosinophilia, and mucus hyperproduction in mice infected initially as neonates. These findings support a pathogenic role for IL-4R alpha on Th cells following RSV reinfection of mice initially infected as neonates; more importantly, our data from human cells suggest that the same mechanism occurs in humans.
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