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 acquired recently, and highlight the role of Type I IFN in Th1 generation, by 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 and the circumstances under which IFN-alpha is produced, in the absence of viral infections. Human dendritic cells (DC) were co-cultured with autologous 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 large amounts (>200 IU IFN-alpha from 2.5x10(4) cells) of IFN-alpha are produced by DC following interaction with stimulated T cells. Similar effects were observed when DC were cultured with CD40L-expressing transfectants, although the amount of IFN-alpha produced was reduced, suggesting that the CD40-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 infection but also during an immunological interaction and this may be the basic mechanism that assists in the development of a Th1 response.
Foster
G R
GR
Department of Medicine, ICSM, St. Mary's Hospital, London, GB. g.foster@ic.ac.uk
Germain
C
C
Jones
M
M
Lechler
R I
RI
Lombardi
G
G
D000818:Animals; D017951:Antigen Presentation; D019013:CD40 Antigens / Q000276:immunology; D023201:CD40 Ligand / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D019013:CD40 Antigens; D016898:Interferon-alpha; D023201:CD40 Ligand