Cutting edge: IL-18-transgenic mice: in vivo evidence of a broad role for IL-18 in modulating immune function.
IL-18 has been shown to be a strong cofactor for Th1 T cell development. However, we previously demonstrated that when IL-18 was combined with IL-2, there was a synergistic induction of a Th2 cytokine, IL-13, in both T and NK cells. More recently, we and other groups have reported that IL-18 can potentially induce IgE, IgG1, and Th2 cytokine production in murine experimental models. Here, we report on the generation of IL-18-transgenic (Tg) mice in which mature mouse IL-18 cDNA was expressed. CD8+CD44high T cells and macrophages were increased, but B cells were decreased in these mice while serum IgE, IgG1, IL-4, and IFN-gamma levels were significantly increased. Splenic T cells in IL-18 Tg mice produced higher levels of IFN-gamma, IL-4, IL-5, and IL-13 than control wild-type mice. Thus, aberrant expression of IL-18 in vivo results in the increased production of both Th1 and Th2 cytokines.
Hoshino
T
T
Department of Internal Medicine 1, Kurume University, Kurume, Japan. hoshino@med.kurume-u.ac.jp
Kawase
Y
Y
Okamoto
M
M
Yokota
K
K
Yoshino
K
K
Yamamura
K
K
Miyazaki
J
J
Young
H A
HA
Oizumi
K
K
D000276:Adjuvants, Immunologic / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D002452:Cell Count; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000276:immunology; D006131:Growth Inhibitors / Q000235:genetics / Q000502:physiology; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D018793:Interleukin-13 / Q000096:biosynthesis; D020382:Interleukin-18 / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000097:blood; D015848:Interleukin-5 / Q000096:biosynthesis; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D019076:Transgenes / Q000276:immunology*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D000276:Adjuvants, Immunologic; D006131:Growth Inhibitors; D007074:Immunoglobulin G; D018793:Interleukin-13; D020382:Interleukin-18; D015848:Interleukin-5; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma