期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 192, 期 6, 页码 823-833出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.192.6.823
关键词
granulocyte/macrophage colony-stimulating factor; homodimeric interleukin 12; T helper type 1; T helper type 2; interferon gamma
Interleukin (IL)-12 may be secreted as a bioactive T helper type 1 (Th1) cell-inducing heterodimer, as a monomer, or as an antagonistic homodimer. We analyzed the IL-12 produced by mouse splenic dendritic cells (DCs), human thymic DCs, and cultured human monocyte-derived DCs. IL-12 production required both a microbial or T cell-derived stimulus and an appropriate cytokine milieu. The different IL-12 forms were differentially regulated by the cytokines present rather than the stimulus used. IL-4 alone or together with granulocyte/macrophage colony-stimulating factor or interferon gamma effectively enhanced the production of the bioactive heterodimer and selectively reduced the antagonistic homodimer of IL-12. Therefore, IL-4, the major Th2-driving cytokine, provides a negative feedback causing DCs to produce the major Th1-inducing cytokine, bioactive IL-12.
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