An Essential Role for IL-18 in CD8 T Cell-Mediated Suppression of IgE Responses

Abstract

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.

Protective Efficacy of a Toxoplasma gondii Rhoptry Protein 13 Plasmid DNA Vaccine in Mice

“…3). This was consistent with the results of previous studies that used IL-18 as an adjuvant in DNA vaccines, enhancing the development of Th1-driven antigen-specific T helper and cytolytic immune responses (9,19). Therefore, IL-18 appears to be a broadly effective Th1 adjuvant that could be useful in the development of vaccines against toxoplasmosis.…”

CD8+ T Cells Negatively Regulate IL-4–Dependent, IgG1-Dominant Posttransplant Alloantibody Production

“…While it is generally appreciated that CD4 + T cells and B cells collaborate for antibody production, we and others have noted a novel inhibitory function of CD8 + T cells manifested by the negative regulation of antibody production. Depletion of CD8 + T cells has been shown to significantly increase antigen specific antibody production in models of transplantation, allergy, bacterial infection, viral infection, and platelet transfusion (12-19). In our model, alloantibodies mediate in vivo allospecific cytotoxicity and acute hepatocellular allograft damage by a macrophage-dependent mechanism (20).…”

Immune response to aTrichinella spiralisinfection in house mice from lines selectively bred for high voluntary wheel running

“…in the acute state of infection) were used to assess the primary immune response to infection. Two weeks post-infection is the predicted time of maximum IgE response (Jarrett and Haig, 1976;Dearman et al, 1998;Salagianni et al, 2007;Gurish et al, 2004). A double antibody enzyme-linked sandwich immunoperoxidase assay (Mouse IgE ELISA Kit E90-E; Immunology Consultants Laboratory, Portland, OR, USA) was used to determine plasma IgE levels.…”