S-Space College of Medicine/School of Medicine (의과대학/대학원) Immunology (면역학전공) Journal Papers (저널논문_면역학전공)
IL-4-secreting NKT cells prevent hypersensitivity pneumonitis by suppressing IFN-gamma-producing neutrophils
- Hwang, S. J.; Kim, S.; Park, W. S.; Chung, D. H.
- Issue Date
- American Association of Immunologists
- J Immunol. 2006 Oct 15;177(8):5258-68.
- Alveolitis, Extrinsic Allergic/*etiology/immunology/microbiology; Animals; Antigens, CD1; Antigens, CD1d; CD8-Positive T-Lymphocytes; *Cell Communication; 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
- 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.
- 0022-1767 (Print)
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