Modulation of the allergen-induced human IgE response in Hu-SCID mice: inhibitory effect of human recombinant IFN-gamma and allergen-derived lipopeptide

• Published in: European cytokine network (Montrouge) Vol. 12; no. 3; p. 453
• Main Authors: Duez, C, Gras-Masse, H, Hammad, H, Akoum, H, Didierlaurent, A, André, C, Tonnel, A B, Pestel, J
• Format: Journal Article
• Language: English
• Published: France 01-07-2001
• Subjects: Animals; Antigens, Dermatophagoides; Glycoproteins - immunology; Glycoproteins - pharmacology; Humans; Hypersensitivity - immunology; Immunization; Immunoglobulin E - biosynthesis; Immunoglobulin E - drug effects; Immunoglobulin E - immunology; Interferon-gamma - immunology; Interferon-gamma - pharmacology; Leukocytes, Mononuclear - immunology; Lipoproteins - pharmacology; Mice; Mice, SCID - immunology; Mites - immunology; Models, Animal; Recombinant Proteins
• ISSN: 1148-5493

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.