γδ T cells protect against LPS-induced lung injury

gamma delta T lymphocytes are a unique T cell population with important anti-inflammatory capabilities. Their role in acute lung injury, however, is poorly understood but may provide significant insight into lung-protective mechanisms occurring after injury. In a murine model of lung injury, wild-type C57BL/6 and TCR delta(-/-) mice were exposed to Escherichia coli LPS, followed by analysis of gd T cell and macrophage subsets. In the absence of gd T cells, TCR delta(-/-) mice developed increased inflammation and alveolar-capillary leak compared with wild-type C57BL/6 mice after LPS exposure that correlated with expansion of distinct macrophage populations. Classically activated M1 macrophages were increased in the lung of TCR delta(-/-) mice at d 1, 4, and 7 after LPS exposure that peaked at d 4 and persisted at d 7 compared with wild-type animals. In response to LPS, V gamma 1 and V gamma 7 gamma delta T cells were expanded in the lung and expressed IL-4. Coculture experiments showed decreased expression of TNF-alpha by resident alveolar macrophages in the presence of gamma delta T cells that was reversed in the presence of an anti-IL-4-blocking antibody. Treatment of mice with rIL4 resulted in reduced numbers of M1 macrophages, inflammation, and alveolar-capillary leak. Therefore, one mechanism by which V gamma 1 and V gamma 7 gamma delta T cells protect against LPS-induced lung injury is through IL-4 expression, which decreases TNF-alpha production by resident alveolar macrophages, thus reducing accumulation of M1 macrophages, inflammation, and alveolar-capillary leak.