Human T cells elicit IFN-alpha secretion from dendritic cells following cell to cell interactions

Major insights into events that control Th1/Th2 differentiation have been a cquired recently, and highlight the role of Type I IFN in Th1 generation, b y inducing up-regulation of the IL-12 receptor beta (2) subunit. IFN-alpha induces responsiveness to IL-12, and here we have investigated the source a nd the circumstances under which IFN-alpha is produced, in the absence of v iral infections. Human dendritic cells (DC) were co-cultured with autologou s T cells activated by cross-linking the CD3 complex. DC were also cultured with L cells expressing human CD40 ligand (CD40L). Our results show that l arge amounts (>200 IU IFN-alpha from 2.5x10(4) cells) of IFN-alpha are prod uced by DC following interaction with stimulated T cells. Similar effects w ere observed when DC were cultured with CD40L-expressing transfectants, alt hough the amount of IFN-alpha produced was reduced, suggesting that the CD4 0-CD40L interaction may be important. These results show that stimulated T cells can solicit the signals from DC that allow their polarization towards a Th1 phenotype. Type I DC produce Type I IFN not only following viral inf ection but also during an immunological interaction and this may be the bas ic mechanism that assists in the development of a Th1 response.