Pulmonary V4+ T Cells Have Proinflammatory and Antiviral Effects in Viral Lung Disease

Dodd, J.; Riffault, S.; Kodituwakku, J.S.; Hayday, A.C.; Openshaw, P.J.M.

The Journal of Immunology 182(2): 1174-1181

2009


DOI: 10.4049/jimmunol.182.2.1174
Accession: 068491234

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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.