Title: IL-4Rα on CD4+ T cells plays a pathogenic role in respiratory syncytial virus reinfection in mice infected initially as neonates.
Authors: You, Dahui; Marr, Nico; Saravia, Jordy; Shrestha, Bishwas; Lee, Greg I; Turvey, Stuart E; Brombacher, Frank; Herbert, De'Broski R; Cormier, Stephania A
Published In J Leukoc Biol, (2013 Jun)
Abstract: 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-4Rα 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 Il4ra 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-4Rα 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.
PubMed ID: 23543769
MeSH Terms: Animals; Animals, Newborn; CD4-Positive T-Lymphocytes/immunology; Cytokines/analysis; Cytokines/biosynthesis; Cytokines/immunology; Flow Cytometry; Humans; Interleukin-4 Receptor alpha Subunit/immunology*; Mice; Mice, Inbred BALB C; Respiratory Syncytial Virus Infections/immunology*; Respiratory Syncytial Virus Infections/pathology; Respiratory Syncytial Viruses/immunology; Th2 Cells/immunology*