期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：13
页码：7749-7754
DOI：10.1073/pnas.1332767100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：IFN-{gamma} is well known as the signature cytokine of CD4+ T helper 1, CD8+, and natural killer cells, but recent studies demonstrate that antigen-presenting cells, in particular dendritic cells (DCs), are another potent source for this proinflammatory cytokine. T-bet, a transcription factor that controls IFN-{gamma} expression in CD4+ T cells, was reported recently to be expressed in human monocytes and myeloid DCs. In this study we investigate the role of T-bet in this important cell type. The development, differentiation, and activation of bone marrow and splenic DCs were unimpaired in mice lacking T-bet. However, T-bet was essential for the optimal production of IFN-{gamma} by both CD8+ and CD8- DCs. T-bet-deficient DCs were significantly impaired in their capacity to secrete IFN-{gamma} after both stimulation with IL-12 alone or in combination with IL-18. Further, T-bet-/- DCs were impaired in their ability to activate the T helper 1 program of adoptively transferred antigen-specific T cells in vivo. The rapid up-regulation of T-bet by IFN-{gamma} in DCs coupled with a function for DC-derived IFN-{gamma} in T cell activation may constitute a positive feedback loop to maximize type 1 immunity.
