title: The relative contribution of IL-4 and IL-13 to human IgE synthesis induced by activated CD4+ or CD8+ T cells.
abstract: The relative contribution of IL-4 and IL-13 to the regulation of IgE synthesis has remained relatively poorly characterized, partially because of lack of suitable animal models. We have studied the roles of IL-4 and IL-13 in human IgE synthesis induced by supernatants derived from activated CD4+ or CD8+ T cell clones. Neutralizing anti-IL-4 and anti-IL-13 monoclonal antibodies (mAbs) inhibited IgE synthesis induced by anti-CD40 mAbs and supernatants from CD4+ T cells by an average 61% and 42%, respectively (n = 25). Recombinant IL-13 had additive effects on IL-4-induced IgE synthesis, but only when IL-4 was present at low concentrations. Accordingly, IL-4 was the dominant IgE synthesis-inducing cytokine derived from highly polarized T helper (TH)2 cells. However, anti-IL-13 mAbs also significantly inhibited IgE synthesis induced by two of three supernatants derived from allergen-specific T(H2)-like cell lines generated from the skin of patients with atopic dermatitis. Furthermore, anti-IL-13 mAbs almost completely inhibited IgE synthesis induced by supernatants from T(H1) cells or CD8+ T cell clones. Taken together, these data indicate that IL-13, in addition to IL-4, contributes to IgE synthesis induced by all T helper cell subsets, including allergen-specific T(H2) cells. Moreover, IL-13 appears to be the major IgE synthesis-inducing cytokine derived from T(H1) cells or CD8+ T cells.
authors.affiliation: Human Immunology Department, DNAX Research Institute of Molecular and Cellular Biology, Inc., Palo Alto, CA 94304-1104, USA.
authors.forename: J
authors.initials: J
authors.lastname: Punnonen
authors.forename: H
authors.initials: H
authors.lastname: Yssel
authors.forename: J E
authors.initials: JE
authors.lastname: de Vries
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001667:Binding, Competitive / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D019013:CD40 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D002460:Cell Line; D002474:Cell-Free System / Q000276:immunology; D002999:Clone Cells; D004306:Dose-Response Relationship, Immunologic; D004357:Drug Synergism; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D018793:Interleukin-13 / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D008213:Lymphocyte Activation; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D018793:Interleukin-13; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma