| First Author | Knudson CJ | Year | 2015 |
| Journal | PLoS Pathog | Volume | 11 |
| Issue | 3 | Pages | e1004757 |
| PubMed ID | 25769044 | Mgi Jnum | J:248096 |
| Mgi Id | MGI:5917379 | Doi | 10.1371/journal.ppat.1004757 |
| Citation | Knudson CJ, et al. (2015) RSV vaccine-enhanced disease is orchestrated by the combined actions of distinct CD4 T cell subsets. PLoS Pathog 11(3):e1004757 |
| abstractText | There is no currently licensed vaccine for respiratory syncytial virus (RSV) despite being the leading cause of lower respiratory tract infections in children. Children previously immunized with a formalin-inactivated RSV (FI-RSV) vaccine exhibited enhanced respiratory disease following natural RSV infection. Subsequent studies in animal models have implicated roles for CD4 T cells, eosinophils and non-neutralizing antibodies in mediating enhanced respiratory disease. However, the underlying immunological mechanisms responsible for the enhanced respiratory disease and other disease manifestations associated with FI-RSV vaccine-enhanced disease remain unclear. We demonstrate for the first time that while CD4 T cells mediate all aspects of vaccine-enhanced disease, distinct CD4 T cell subsets orchestrate discrete and specific disease parameters. A Th2-biased immune response, but not eosinophils specifically, was required for airway hyperreactivity and mucus hypersecretion. In contrast, the Th1-associated cytokine TNF-alpha was necessary to mediate airway obstruction and weight loss. Our data demonstrate that individual disease manifestations associated with FI-RSV vaccine-enhanced disease are mediated by distinct subsets of CD4 T cells. |
