Interferon-γ Added During Bacillus Calmette-Guerin Induced Dendritic Cell Maturation Stimulates Potent Th1 Immune Responses

摘要

Dendritic cells (DC) are increasingly prepared in vitro for use in immunotherapy trials. Mature DC express high levels of surface molecules needed for T cell activation and are superior at antigen-presentation than immature DC. Bacillus Calmette-Guerin (BCG) is one of several products known to induce DC maturation, and interferon (IFN)-γ has been shown to enhance the activity of DC stimulated with certain maturation factors. In this study, we investigated the use of IFN-γ in combination with the powerful maturation agent, BCG. The treatment of immature DC with IFN-γ plus BCG led to the upregulation of CD54, CD80, and CD86 in comparison with BCG treatment alone. In MLR or recall immune responses, the addition of IFN-γ at the time of BCG-treatment did not increase the number of antigen-specific T cells but enhanced the development of IFN-γ-producing Th1 cells. In primary immune responses, on the other hand, BCG and IFN-γ co-treated DC stimulated higher proportions of specific T cells as well as IFN-γ secretion by these T cells. Thus the use of IFN-γ during BCG-induced DC maturation differentially affects the nature of recall versus naïve antigen-specific T-cell responses. IFN-γ co-treatment with BCG was found to induce IL-12 and, in some instances, inhibit IL-10 secretion by DC. These findings greatly enhance the potential of BCG-matured dendritic cells for use in cancer immunotherapy.