RRC ID 11856
Author Segawa S, Goto D, Yoshiga Y, Horikoshi M, Sugihara M, Hayashi T, Chino Y, Matsumoto I, Ito S, Sumida T.
Title Involvement of NK 1.1-positive γδT cells in interleukin-18 plus interleukin-2-induced interstitial lung disease.
Journal Am J Respir Cell Mol Biol
Abstract Interstitial lung disease (ILD) is induced by various factors in humans. However, the exact mechanism of ILD remains elusive. This study sought to determine the role of natural killer (NK) 1.1(+) γδT cells in ILD. The injection of IL-18 plus IL-2 (IL-18/IL-2) into C57BL6 (B6) mice induced acute ILD that resembled early-stage human ILD. An accumulation of NK1.1(+) γδT cells similar to NK cells was evident in the lungs. The T Cell Receptor (TCR) Vγ and Vδ repertoires of NK1.1(+) γδT cells indicated polyclonal expansion. The expression of IL-2 receptor β (Rβ) and IL-18Rβ in NK1.1(+) γδT cells was higher than in NK1.1(-) γδT cells. IL-18/IL-2 stimulated the proliferation of NK1.1(+) γδT cells, but not NK1.1(-) γδT cells. The IL-18/IL-2-stimulated NK1.1(+) γδT cells produced higher concentrations of IFN-γ than did NK1.1(-) γδT cells. Moreover, NK1.1(+) γδT and NK1.1(-) γδT cells constituted completely different cell populations. The IL-18/IL-2-induced ILD was milder in TCRδ(-/-) and IFN-γ(-/-) mice, compared with B6 mice. Furthermore, cell-transfer experiments demonstrated that NK1.1(+) γδT cells could induce the expansion of NK cells and IFN-γ mRNA in the lung by IL-18/IL-2. Our results suggest that NK1.1(+) γδT cells function as inflammatory mediators in the early phase of IL-18/IL-2-induced ILD.
Volume 45(3)
Pages 659-66
Published 2011-9-1
DOI 10.1165/rcmb.2010-0298OC
PII 2010-0298OC
PMID 21257923
MeSH Animals Antigens, Ly / biosynthesis* Antigens, Ly / genetics Female Gene Expression Regulation* Humans Inflammation Interferon-gamma / metabolism Interleukin-18 / metabolism* Interleukin-2 / metabolism* Killer Cells, Natural / cytology Liver / metabolism Lung / metabolism Lung Diseases, Interstitial / metabolism* Mice Mice, Inbred C57BL Models, Biological NK Cell Lectin-Like Receptor Subfamily B / biosynthesis* NK Cell Lectin-Like Receptor Subfamily B / genetics Receptors, Antigen, T-Cell, gamma-delta / metabolism* Recombinant Proteins / chemistry Spleen / metabolism
IF 5.373
Times Cited 7
Mice RBRC00407