In vivo administration of IL-18 can induce IgE production through Th2 cytokine induction and up-regulation of CD40 ligand (CD154) expression on CD4+ T cells.
IL-18 is considered to be a strong cofactor for CD4+ T helper 1 (Th1) cell induction. We have recently reported that IL-18 can induce IL-13 production in both NK cells and T cells in synergy with IL-2 but not IL-12, suggesting IL-18 can induce Th1 and Th2 cytokines when accompanied by the appropriate first signals for T cells. We have now found that IL-18 can act as a cofactor to induce IL-4, IL-10 and IL-13 as well as IFN-gamma production in T cells in the presence of anti-CD3 monoclonal antibodies (mAb). IL-18 can rapidly induce CD40 ligand (CD154) mRNA and surface expression on CD4+ but not CD8+ T cells. The administration of IL-18 alone in vivo significantly increased serum IgE levels in C57BL/6 (B6) and B6 IL-4 knockout mice. Furthermore, the administration of IL-18 plus IL-2 induced approximately 70-fold and 10-fold higher serum levels of IgE and IgG1 than seen in control B6 mice, respectively. IgE and IgG1 induction in B6 mice by administration of IL-18 plus IL-2 was eliminated by the pretreatment of mice with anti-CD4 or anti-CD154, but not anti-CD8 or anti-NK1.1 mAb. These results suggest that IL-18 can induce Th2 cytokines and CD154 expression, and can contribute to CD4+ T cell-dependent, IL-4-independent IgE production.
Laboratory of Experimental Immunology, DBS, NCI-FCRDC, Frederick, USA. hoshino@med.kurume-u.ac.jp
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Hoshino
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Yagita
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Ortaldo
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Wiltrout
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Young
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000941:Antigens / Q000276:immunology; D000950:Antigens, Ly; D000954:Antigens, Surface; D017252:CD3 Complex / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D023201:CD40 Ligand; D016827:CD8 Antigens / Q000276:immunology; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007274:Injections, Intraperitoneal; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000276:immunology; D018793:Interleukin-13 / Q000096:biosynthesis* / Q000276:immunology; D020382:Interleukin-18 / Q000008:administration & dosage / Q000276:immunology*; D007376:Interleukin-2 / Q000008:administration & dosage; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins / Q000276:immunology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D015398:Signal Transduction; D018418:Th2 Cells / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000941:Antigens; D000950:Antigens, Ly; D000954:Antigens, Surface; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D007074:Immunoglobulin G; D018793:Interleukin-13; D020382:Interleukin-18; D007376:Interleukin-2; C527203:KLRB1 protein, human; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D011994:Recombinant Proteins; D016753:Interleukin-10; D023201:CD40 Ligand; D015847:Interleukin-4; D007073:Immunoglobulin E