Pulmonary Vγ4+ γδ T Cells Have Proinflammatory and Antiviral Effects in Viral Lung Disease

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 bronchiotitis worldwide. The role of alpha beta 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 V gamma 7(+) gamma delta T cells were present; however, immunization with a live vaccinia vector expressing RSV F protein substantially enhanced V gamma 4(+) gamma delta 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 gamma delta T cells in vivo reduced lung inflammation and disease severity and slightly increased peal, viral replication but did not prevent viral clearance. These studies demonstrate a novel role for gamma delta T cells in the development of immunopathology and cellular influx into the lungs after immunization and RSV challenge. Though a minor population, gamma delta T cells have a critical influence on disease and are an attractive interventional target in the alleviation of viral lung disease. The Journal of Immunology, 2009, 182: 1174-1181.