IL-12 stimulates an antiviral type 1 cytokine response but lacks adjuvant activity in IFN-gamma-receptor-deficient mice. 1995

V E Schijns, and B L Haagmans, and M C Horzinek
Department of Infectious Diseases and Immunology, Veterinary Faculty, Ultrecht University, The Netherlands.

Cytokines can be used as adjuvants to enhance and direct protective immune responses induced by vaccines. IL-12, a cytokine that favors the maturation of Th1-type cells and stimulates associated cell-mediated responses was evaluated as immunologic adjuvant for a viral vaccine in a mouse challenge model. When it was administered together with inactivated pseudorabies virus, a herpes simplex virus related alpha-herpesvirus, increased production of IFN-gamma by ex vivo-stimulated splenocytes was observed as well as augmented production of antiviral serum lgG2a. This was associated with increased protection against a lethal challenge infection. Infection of IfN-gamma-neutralizing Ab reduced the increased antiviral resistance in IL-12-treated mice. Also, in mice bearing an inactivated IFN-gamma-receptor gene IL-12 failed to stimulate protection against challenge and the synthesis of antiviral lgG2a. However, in these IFN-gamma-receptor knockout mice, increased antiviral lgG2b levels and enhanced IFN-gamma-secretion, with minimal IL-4 production, by ex vivo-stimulated splenocytes was observed. In wild-type mice administration of recombinant IFN-gamma but not IL-2 mimicked the immune-stimulating activity of IL-12; it is therefore likely that the IL-12 adjuvant activity is largely mediated by physiologic IFN-gamma.

UI MeSH Term Description Entries
D007074 Immunoglobulin G The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B. Gamma Globulin, 7S,IgG,IgG Antibody,Allerglobuline,IgG(T),IgG1,IgG2,IgG2A,IgG2B,IgG3,IgG4,Immunoglobulin GT,Polyglobin,7S Gamma Globulin,Antibody, IgG,GT, Immunoglobulin
D007371 Interferon-gamma The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES. Interferon Type II,Interferon, Immune,gamma-Interferon,Interferon, gamma,Type II Interferon,Immune Interferon,Interferon, Type II
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008817 Mice, Mutant Strains Mice bearing mutant genes which are phenotypically expressed in the animals. Mouse, Mutant Strain,Mutant Mouse Strain,Mutant Strain of Mouse,Mutant Strains of Mice,Mice Mutant Strain,Mice Mutant Strains,Mouse Mutant Strain,Mouse Mutant Strains,Mouse Strain, Mutant,Mouse Strains, Mutant,Mutant Mouse Strains,Mutant Strain Mouse,Mutant Strains Mice,Strain Mouse, Mutant,Strain, Mutant Mouse,Strains Mice, Mutant,Strains, Mutant Mouse
D011558 Herpesvirus 1, Suid A species of VARICELLOVIRUS producing a respiratory infection (PSEUDORABIES) in swine, its natural host. It also produces an usually fatal ENCEPHALOMYELITIS in cattle, sheep, dogs, cats, foxes, and mink. Aujeszky's Disease Virus,Swine Herpesvirus 1,Aujeszky Disease Virus,Herpesvirus 1 (alpha), Suid,Herpesvirus Suis,Pseudorabies Virus,Suid Herpesvirus 1,Aujeszkys Disease Virus,Herpesvirus 1, Swine,Pseudorabies Viruses,Virus, Pseudorabies,Viruses, Pseudorabies
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D005260 Female Females
D000096743 Interferon gamma Receptor A heterodimeric receptor composed of two subunits IFNGR1 and IFNGR2. Activated IFNGR1 subunit is believed to form a docking site for SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION 1 (STAT1). IFNGR2 associates with IFNGR1 to form a receptor for the cytokine interferon gamma (IFNG). CD119 Antigen,CDw119 Antigen,IFN-gamma Receptor 1,IFNGR2 Protein,Interferon gamma Receptor 2,Interferon gamma Receptors,Receptor, Interferon gamma,IFN-gammaR,1, IFN-gamma Receptor,Antigen, CD119,Antigen, CDw119,IFN gamma Receptor 1,IFN gammaR,Protein, IFNGR2,Receptor 1, IFN-gamma,Receptors, Interferon gamma,gamma Receptor, Interferon,gamma Receptors, Interferon
D000276 Adjuvants, Immunologic Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (Freund's adjuvant, BCG, Corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity. Immunoactivators,Immunoadjuvant,Immunoadjuvants,Immunologic Adjuvant,Immunopotentiator,Immunopotentiators,Immunostimulant,Immunostimulants,Adjuvant, Immunologic,Adjuvants, Immunological,Immunologic Adjuvants,Immunological Adjuvant,Adjuvant, Immunological,Immunological Adjuvants

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