title: Human eosinophils produce biologically active IL-12: implications for control of T cell responses.
abstract: The present study assessed the capacity of eosinophils (EOS) to synthesize the cytokine IL-12. Blood-derived, highly purified human EOS from six atopic patients and two nonatopic individuals were treated in culture with IL-4, IL-5, granulocyte-macrophage CSF, IFN-gamma, TNF-alpha, IL-1alpha, RANTES, and complement 5a, respectively. The expression of both IL-12 protein and mRNAs for the p35 and p40 IL-12 subunits was strongly induced in all donors by the Th2-like cytokines IL-4 and granulocyte-macrophage CSF and was also moderately induced by TNF-alpha and IL-1alpha. IL-5 treatment resulted in IL-12 synthesis in four atopic donors and one nonatopic donor, whereas IFN-gamma induced IL-12 synthesis in only two atopic donors. In contrast, RANTES exclusively induced mRNA for the p40 subunit without detectable protein release, and complement 5a had no effect on IL-12 mRNA or protein expression. EOS-derived IL-12 was biologically active, because supernatants derived from IL-4-treated EOS superinduced the Con A-induced expression of IFN-gamma by a human Th1-like T cell line. This activity was neutralized by anti-IL-12 Abs. In conclusion, EOS secrete biologically active IL-12 after treatment with selected cytokines, which mainly represent the Th2-like type. Consequently, EOS may promote a switch from Th2-like to Th1-like immune responses in atopic and parasitic diseases.
authors.affiliation: Department of Dermatology, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Grewe
authors.forename: W
authors.initials: W
authors.lastname: Czech
authors.forename: A
authors.initials: A
authors.lastname: Morita
authors.forename: T
authors.initials: T
authors.lastname: Werfel
authors.forename: M
authors.initials: M
authors.lastname: Klammer
authors.forename: A
authors.initials: A
authors.lastname: Kapp
authors.forename: T
authors.initials: T
authors.lastname: Ruzicka
authors.forename: E
authors.initials: E
authors.lastname: Schöpf
authors.forename: J
authors.initials: J
authors.lastname: Krutmann
mesh_terms: D002460:Cell Line; D002474:Cell-Free System / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000302:isolation & purification / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D018664:Interleukin-12; D007371:Interferon-gamma