Production of IL-13 in spleen cells by IL-18 and IL-12 through generation of NK-like cells.
Treatment of Nylon wool-passed cells (NWC) prepared from the spleen of C57BL/6 mice with IL-18 and IL-12, but not with IL-18 alone, resulted in induction of IFN-gamma, a Th1 cytokine, and GM-CSF at 24 h, and IL-13, a Th2 cytokine at 72 h. The induction of IL-13 was suppressed by anti-GM-CSF antibody, indicating involvement of GM-CSF in IL-13 production. When NWC incubated with IL-18 and IL-12 for 72 h ("primary treatment") were treated again with the same cytokines ("secondary treatment"), IL-13 was induced much more quickly than observed in the primary treatment. Flow cytometric analysis of NWC after the primary treatment showed marked increases in the CD4(-)CD8(-) non-T cell population bearing CD25(+), CD45RB(super high) and CD122(+). These cells were positive for CD49b but negative for NK1.1, indicating that they were not typical but NK-like cells. The NK-like cells produced IL-13 in response to the treatment with IL-18 alone, indicating that the generation of these cells in the primary treatment likely accounts for the quick production of IL-13 in the secondary treatment. These results show that IL-18 and IL-12 generates the NK-like cells in NWC by a process mediated by GM-CSF that are ready for producing IL-13.
Laboratory of Host Defenses, Institute for Advanced Medical Sciences, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
Haruyasu
H
Ueda
Shin-ichiro
S
Kashiwamura
Atsuo
A
Sekiyama
Takeharu
T
Ogura
Naomi
N
Gamachi
Haruki
H
Okamura
D000818:Animals; D000906:Antibodies / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D002469:Cell Separation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology*; D018793:Interleukin-13 / Q000276:immunology*; D020382:Interleukin-18 / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D015375:Receptors, Interleukin-2 / Q000276:immunology; D013154:Spleen / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology
D000906:Antibodies; D015704:CD4 Antigens; D016827:CD8 Antigens; D018793:Interleukin-13; D020382:Interleukin-18; D015375:Receptors, Interleukin-2; D018664:Interleukin-12; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor