title: Pulmonary V gamma 4+ gamma delta T cells have proinflammatory and antiviral effects in viral lung disease.
abstract: Host defenses, while effecting viral clearance, contribute substantially to inflammation and disease. This double action is a substantial obstacle to the development of safe and effective vaccines against many agents, particularly respiratory syncytial virus (RSV). RSV is a common cold virus and the major cause of infantile bronchiolitis worldwide. The role of alphabeta T cells in RSV-driven immunopathology is well studied, but little is known about the role of "unconventional" T cells. During primary RSV challenge of BALB/c mice, some Vgamma7+ gammadelta T cells were present; however, immunization with a live vaccinia vector expressing RSV F protein substantially enhanced Vgamma4+ gammadelta T cell influx after RSV infection. Harvested early, these cells produced IFN-gamma, TNF, and RANTES after ex vivo stimulation. By contrast, those recruited 5 days after challenge made IL-4, IL-5, and IL-10. Depletion of gammadelta T cells in vivo reduced lung inflammation and disease severity and slightly increased peak viral replication but did not prevent viral clearance. These studies demonstrate a novel role for gammadelta T cells in the development of immunopathology and cellular influx into the lungs after immunization and RSV challenge. Though a minor population, gammadelta T cells have a critical influence on disease and are an attractive interventional target in the alleviation of viral lung disease.
authors.affiliation: Center for Respiratory Infections, National Heart and Lung Institute, St. Mary's Campus, Imperial College London, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Dodd
authors.forename: Sabine
authors.initials: S
authors.lastname: Riffault
authors.forename: Jayanie S
authors.initials: JS
authors.lastname: Kodituwakku
authors.forename: Adrian C
authors.initials: AC
authors.lastname: Hayday
authors.forename: Peter J M
authors.initials: PJ
authors.lastname: Openshaw
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects; D000818:Animals; D002465:Cell Movement / Q000276:immunology; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology*; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D008213:Lymphocyte Activation / Q000276:immunology; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis / Q000502:physiology*; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D012720:Severity of Illness Index; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014760:Viral Fusion Proteins / Q000008:administration & dosage / Q000276:immunology; D014779:Virus Replication / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D018836:Inflammation Mediators; D016692:Receptors, Antigen, T-Cell, gamma-delta; D022261:Respiratory Syncytial Virus Vaccines; D014614:Vaccines, Synthetic; D014760:Viral Fusion Proteins