Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 35, Issue 6, Pages 1928-1938Publisher
WILEY-BLACKWELL
DOI: 10.1002/eji.200425762
Keywords
neutrophils; hypersensitivity pneurnonitis; IFN-gamma; RAG-1(-/-)
Categories
Funding
- NCI NIH HHS [CA21765] Funding Source: Medline
- PHS HHS [A1053137] Funding Source: Medline
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Hypersensitivity pneumonitis (HP) is an interstitial lung disease that develops following repeated exposure to inhaled particulate antigens. The disease is characterized by lymphocytic alveolitis, granuloma formation and fibrosis. IFN-gamma is required for the formation of granulomas in HP, and we therefore focused on identifying the cellular sources of IFN-gamma during the disease. Using the Saccharopolyspora rectivirgula (SR) animal model of HP, we demonstrated that the majority of IFN-gamma(+) cells in the lung following SR exposure are neutrophils. Ab-mediated depletion of neutrophils in mice prior to exposure to SR resulted in a decrease in the level of IFN-gamma mRNA and protein compared to isotype Ab-treated mice, suggesting that neutrophils are an important source of IFN-gamma during HP. To determine the contribution of T and non-T cell sources of IFN-gamma to granuloma formation, we performed adoptive transfer studies. RAG-1(-/-) mice reconstituted with spleen cells from IFN-gamma(-/-) mice developed granulomas similarly to RAG-1(-/-) mice reconstituted with normal spleen cells. Therefore innate immune cell IFN-gamma production in the absence of T cell IFN-gamma production is sufficient for granuloma formation. These results provide new insight into the pathogenesis of HP and demonstrate the important contribution of innate immune cells to the disease process.
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