Pulmonary Vγ4+ γδ T cells have proinflammatory and antiviral effects in viral lung disease

J Dodd, S Riffault, JS Kodituwakku… - The Journal of …, 2009 - journals.aai.org
J Dodd, S Riffault, JS Kodituwakku, AC Hayday, PJM Openshaw
The Journal of Immunology, 2009journals.aai.org
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 αβ 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 Vγ7+ γδ T …
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 αβ 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 Vγ7+ γδ T cells were present; however, immunization with a live vaccinia vector expressing RSV F protein substantially enhanced Vγ4+ γδ T cell influx after RSV infection. Harvested early, these cells produced IFN-γ, 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 γδ 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 γδ T cells in the development of immunopathology and cellular influx into the lungs after immunization and RSV challenge. Though a minor population, γδ T cells have a critical influence on disease and are an attractive interventional target in the alleviation of viral lung disease.
journals.aai.org