T Cell Biasing by Activated Dendritic Cells

We have previously reported that the ligation of FcgammaRs on activated macrophages affected their production of cytokines and their ability to influence T cell activation. Dendritic cells (DC) are important APCs that also express FcgammaR. In the present work, we sought to determine whether DC responded to immune complexes in a manner similar to macrophages. We confirmed that activated murine DC produced IL-12, and, as a result, induced naive T cells to produce primarily IFN-gamma upon stimulation. However, DC activated in the presence of immune complexes shut off their production of IL-12p70 and induced a Th2-like cytokine response. Thus, DC respond to immune complexes by altering their cytokine production, which, in turn, influences T cell responses. A DC transfer experiment was performed to determine the extent that APC exposure to immune complexes could influence adaptive immune responses. Vaccination of mice with Ag, along with DC that were activated in the presence of immune complexes, resulted in higher levels of Ag-specific IgG1 Ab, relative to mice that were vaccinated with activated DC and Ag alone. The mechanism by which DC altered their cytokine production in response to immune complexes was different from macrophages. Macrophages down-regulated the transcription of both the p40 and p35 subunits of IL-12, whereas DC decreased only p35 expression. We conclude that APCs expressing FcgammaR on their surface can respond to immune complexes by shutting off IL-12 biosynthesis, to prevent the Th1-type T cell biasing that normally accompanies innate immune activation.