Modulation of the allergen-induced human IgE response in Hu-SCID mice: inhibitory effect of human recombinant IFN-gamma and allergen-derived lipopeptide.
We have previously established a model to study the in vivo human IgE response using humanized SCID mice. Allergic SCID mice were obtained following intraperitoneal injection with mononuclear cells from Dermatophagoides pteronyssinus (Dpt)-sensitive patients, and sensitization by Dpt allergen intraperitoneal injection (immunization) or Dpt aerosol (inhalation). Human serum IgE was measured in allergic SCID mice after administration of human recombinant IFN-gamma or the lipopeptide LP 52-71 (derived from peptide p52-71 from Der p 1, Dpt major allergen, coupled to a lipophilic moiety), during the immunization or the inhalation phase. IFN-gamma inhibited human IgE production when given at the time of immunization, but not during inhalation. This effect was long-lasting as Dpt aerosol, given one month after immunization and IFN-gamma administration, failed to increase IgE levels. Unlike Dpt or p52-71, LP 52-71 failed to induce human IgE production at day 14 and 21 after its injection, but did inhibit the development of the IgE response after a secondary Dpt-challenge. Moreover, LP 52-71 administration 14 days after Dpt inhalation decreased IgE levels, in contrast to peptide 52-71, which increased IgE levels. Thus, taken together these results indicate that the development of the human IgE response in allergic SCID mice can be modulated by modified allergen and a Th1 cytokine.
Duez
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INSERM U. 416 Institut Pasteur de Lille, 1, rue du Pr Calmette, BP 245, 59019 Lille Cedex, France.
Gras-Masse
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Hammad
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Akoum
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H
Didierlaurent
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André
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Tonnel
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Pestel
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D000818:Animals; D039741:Antigens, Dermatophagoides; D006023:Glycoproteins / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D007114:Immunization; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000187:drug effects* / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008074:Lipoproteins / Q000494:pharmacology*; D051379:Mice; D016513:Mice, SCID / Q000276:immunology; D008925:Mites / Q000276:immunology; D023421:Models, Animal; D011994:Recombinant Proteins
D039741:Antigens, Dermatophagoides; D006023:Glycoproteins; D008074:Lipoproteins; D011994:Recombinant Proteins; D007073:Immunoglobulin E; D007371:Interferon-gamma