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IL-4-secreting NKT cells prevent hypersensitivity pneumonitis by suppressing IFN-gamma-producing neutrophils
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- Authors
- Issue Date
- 2006-10-04
- Publisher
- American Association of Immunologists
- Citation
- J Immunol. 2006 Oct 15;177(8):5258-68.
- Keywords
- Alveolitis, Extrinsic Allergic/*etiology/immunology/microbiology ; Animals ; Antigens, CD1 ; Antigens, CD1d ; CD8-Positive T-Lymphocytes ; Cell Proliferation ; Interferon-gamma/biosynthesis/*physiology ; Interleukin-4/*secretion ; Killer Cells, Natural/cytology/*secretion ; Lung/immunology/pathology ; Lymphocyte Activation ; Mice ; Mice, Knockout ; Neutrophils/cytology/*metabolism ; Saccharopolyspora ; T-Lymphocytes ; Cell Communication
- Abstract
- Hypersensitivity pneumonitis (HP) is mediated by Th1 immune response. NKT cells regulate immune responses by modulating the Th1/Th2 balance. Therefore, we postulated that NKT cells play a critical role in the development of the HP by modulating the Th1/Th2 response. To address this issue, we explored the functional roles of NKT cells in Saccharopolyspora rectivirgula (SR)-induced HP. In CD1d(-/-) mice, the HP was worse in terms of histological changes, hydroxyproline levels, the CD4:CD8 ratio in bronchoalveolar lavage fluid, and SR-specific immune responses than in control mice. CD1d(-/-) mice showed elevated IFN-gamma production in the lung during the HP, and this was produced mainly by Gr-1+ neutrophils. The blockade of IFN-gamma in CD1d(-/-) mice attenuated the HP, whereas the injection of rIFN-gamma aggravated it. Moreover, the depletion of Gr-1+ neutrophils reduced CD8+ T cell numbers in bronchoalveolar lavage fluid during the HP. The adoptive transfer of IL-4(-/-) mouse NKT cells did not attenuate the HP, whereas wild-type or IFN-gamma(-/-) mouse NKT cells suppressed the HP. In conclusion, NKT cells producing IL-4 play a protective role in SR-induced HP by suppressing IFN-gamma-producing neutrophils, which induce the activation and proliferation of CD8+ T cells in the lung.
- ISSN
- 0022-1767 (Print)
- Language
- English
- URI
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17015711
https://hdl.handle.net/10371/22591
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