An Ovalbumin-IL-12 Fusion Protein Is More Effective than Ovalbumin Plus Free Recombinant IL-12 in Inducing a T Helper Cell Type 1-Dominated Immune Response and Inhibiting Antigen-Specific IgE Production

Tae Sung Kim, Rosemarie H. DeKruyff, Randall Rupper, Holden T. Maecker, Shoshana Levy, Dale T. Umetsu

Research output: Contribution to journalArticle

159 Citations (Scopus)

Abstract

Optimal treatment of allergic diseases requires that the cytokine profile of allergen-specific T cells be redirected, with the conversion of Th2 profiles into Th1 cytokine profiles. This conversion, however, is difficult, since Th2 effector cells have relatively fixed cytokine profiles. To more effectively redirect the cytokine profiles of T cells, we constructed a cytokine fusion protein that contained the Ag OVA, fused to IL-12. Immunization with the OVA-IL-12 fusion protein induced anti-OVA IgG2a Ab and large quantities of OVA-specific IFN-γ production. The Ag specificity of this response was dependent upon covalent linkage of Ag and IL-12, since immunization of mice with OVA alone induced little or no IFN-γ, while immunization with OVA and free rIL-12 enhanced T cell production of IFN-γ, but the IFN-γ production was not OVA specific. To examine the effects of OVA-IL-12 in reversing ongoing Th2-dominated immune responses, BALB/c mice previously primed with OVA in alum to induce a Th2-dominated response, were vaccinated with the OVA-IL-12 protein. In such mice, OVA-IL-12 was much more effective than OVA plus free rIL-12 in significantly increasing Ag-specific IFN-γ production and significantly decreasing Ag-specific IL-4 production. Moreover, OVA-IL-12 increased serum anti-OVA IgG2a and decreased anti-OVA IgE. These studies indicate that OVA-IL-12 can convert immune responses characterized by high IL-4 and high IgE synthesis into Th1-dominated responses in an Ag-specific manner.

Original languageEnglish
Pages (from-to)4137-4144
Number of pages8
JournalJournal of Immunology
Volume158
Issue number9
Publication statusPublished - 1997 May 1
Externally publishedYes

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Th1 Cells
Histocompatibility Antigens Class II
Ovalbumin
Interleukin-12
Immunoglobulin E
Cytokines
Proteins
Immunization
T-Lymphocytes
Interleukin-4
Th2 Cells
Allergens
Serum

ASJC Scopus subject areas

  • Immunology

Cite this

An Ovalbumin-IL-12 Fusion Protein Is More Effective than Ovalbumin Plus Free Recombinant IL-12 in Inducing a T Helper Cell Type 1-Dominated Immune Response and Inhibiting Antigen-Specific IgE Production. / Kim, Tae Sung; DeKruyff, Rosemarie H.; Rupper, Randall; Maecker, Holden T.; Levy, Shoshana; Umetsu, Dale T.

In: Journal of Immunology, Vol. 158, No. 9, 01.05.1997, p. 4137-4144.

Research output: Contribution to journalArticle

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