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* Department of Asthma, Allergy, and Respiratory Science, King’s College London School of Medicine, London, United Kingdom;
Immunology Center, "Saint Savas" Cancer Hospital, Athens, Greece;
Novartis Institutes for Biomedical Research, Horsham, United Kingdom; and
Immunology Programme and Department of Microbiology, National University of Singapore, Singapore
The ability of CD8 T cells to suppress IgE responses is well established. Previously, we demonstrated that CD8 T cells inhibit IgE responses via the induction of IL-12, which promotes Th1 and suppresses Th2 responses. In this study, we show that IL-18 also plays an essential role in IgE suppression. In vitro, IL-18 synergized with IL-12 to promote Th1/T cytotoxic 1 and inhibit Th2/T cytotoxic 2 differentiation. OVA-specific TCR transgenic (OT-I) CD8 cells induced both IL-12 and IL-18 when cultured with OVA257–264 peptide-pulsed dendritic cells. In vivo, IL-18–/– mice exhibited higher IgE and IgG1 levels compared with wild-type mice after immunization with OVA/alum. Furthermore, adoptive transfer of CD8 T cells from OVA-primed mice suppressed IgE responses in OVA/alum-immunized mice, but not in IL-18–/– mice. IgE suppression in IL-18–/– mice was restored if CD8 T cells were coadoptively transferred with IL-18-competent wild-type bone marrow dendritic cell progenitors, demonstrating an essential role of IL-18 in CD8 T cell-mediated suppression of IgE responses. The data suggest that CD8 T cells induce IL-18 production during a cognate interaction with APCs that synergizes with IL-12 to promote immune deviation away from the allergic phenotype. Our data identify IL-18 induction as a potentially useful target in immunotherapy of allergic disease.
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1 M.S. was supported by a scholarship from Alexander S. Onassis Public Benefit Foundation (Greek section of Scholarships and Research).
2 Address correspondence and reprint requests to Dr. David M. Kemeny, Immunology Programme and Department of Microbiology, Centre for Life Sciences, 28 Medical Drive, National University of Singapore, Singapore 117456. E-mail address: michead{at}nus.edu.sg
3 Abbreviations used in this paper: DC, dendritic cell; BMDCp, bone marrow DC precursor; IRF-1, IFN regulatory factor-1; PCA, passive cutaneous anaphylaxis; Tc1, T cytotoxic 1.
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