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IL-4-secreting NKT cells prevent hypersensitivity pneumonitis by suppressing IFN-gamma-producing neutrophils

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Authors
Hwang, S. J.; Kim, S.; Park, W. S.; Chung, D. H.
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/microbiologyAnimalsAntigens, CD1Antigens, CD1dCD8-Positive T-Lymphocytes*Cell CommunicationCell ProliferationInterferon-gamma/biosynthesis/*physiologyInterleukin-4/*secretionKiller Cells, Natural/cytology/*secretionLung/immunology/pathologyLymphocyte ActivationMiceMice, KnockoutNeutrophils/cytology/*metabolismSaccharopolysporaT-Lymphocytes
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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College of Medicine/School of Medicine (의과대학/대학원)Immunology (면역학전공)Journal Papers (저널논문_면역학전공)
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