Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Animals
-
Antibodies, Monoclonal / immunology
-
Antigens / immunology
-
Antigens, Ly
-
Antigens, Surface
-
CD3 Complex / immunology
-
CD4 Antigens / immunology
-
CD4-Positive T-Lymphocytes / drug effects
-
CD4-Positive T-Lymphocytes / immunology*
-
CD40 Ligand
-
CD8 Antigens / immunology
-
Female
-
Humans
-
Immunoglobulin E / biosynthesis*
-
Immunoglobulin G / biosynthesis
-
Injections, Intraperitoneal
-
Interleukin-10 / biosynthesis*
-
Interleukin-10 / immunology
-
Interleukin-13 / biosynthesis*
-
Interleukin-13 / immunology
-
Interleukin-18 / administration & dosage
-
Interleukin-18 / immunology*
-
Interleukin-2 / administration & dosage
-
Interleukin-4 / biosynthesis*
-
Interleukin-4 / genetics
-
Interleukin-4 / immunology
-
Lectins, C-Type
-
Membrane Glycoproteins / genetics*
-
Mice
-
Mice, Inbred C57BL
-
Mice, Knockout
-
NK Cell Lectin-Like Receptor Subfamily B
-
Proteins / immunology
-
Recombinant Proteins / administration & dosage
-
Recombinant Proteins / immunology
-
Signal Transduction
-
Th2 Cells / immunology*
-
Up-Regulation / immunology*
Substances
-
Antibodies, Monoclonal
-
Antigens
-
Antigens, Ly
-
Antigens, Surface
-
CD3 Complex
-
CD4 Antigens
-
CD8 Antigens
-
Immunoglobulin G
-
Interleukin-13
-
Interleukin-18
-
Interleukin-2
-
KLRB1 protein, human
-
Klrb1c protein, mouse
-
Lectins, C-Type
-
Membrane Glycoproteins
-
NK Cell Lectin-Like Receptor Subfamily B
-
Proteins
-
Recombinant Proteins
-
Interleukin-10
-
CD40 Ligand
-
Interleukin-4
-
Immunoglobulin E