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

Virgil E.C.J. Schijns*, Bart L. Haagmans, Marian C. Horzinek

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

73 Citations (Scopus)

Abstract

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 α-herpesvirus, increased production of IFN- γ by ex vivo-stimulated splenocytes was observed as well as augmented production of antiviral serum IgG2a. This was associated with increased protection against a lethal challenge infection. Injection of IFN-γ- neutralizing Ab reduced the increased antiviral resistance in IL-12-treated mice. Also, in mice bearing an inactivated IFN-γ-receptor gene IL-12 failed to stimulate protection against challenge and the synthesis of antiviral IgG2a. However, in these IFN-γ-receptor knockout mice, increased antiviral IgG2b levels and enhanced IFN-γ secretion, with minimal IL-4 production, by ex vivo-stimulated splenocytes was observed. In wild-type mice administration of recombinant IFN-γ 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-γ.

Original languageEnglish
Pages (from-to)2525-2532
Number of pages8
JournalJournal of Immunology
Volume155
Issue number5
Publication statusPublished - 1 Sept 1995
Externally publishedYes

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