International Immunology Advance Access originally published online on June 7, 2004
International Immunology 2004 16(7):1037-1052; doi:10.1093/intimm/dxh106
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International Immunology, Vol. 16, No. 7, pp. 1037-1052,
July 2004
© 2004 Japanese Society for Immunology
Dendritic cells generated in the presence of interferon-
stimulate allogeneic CD4+ T-cell proliferation: modulation by autocrine IL-10, enhanced T-cell apoptosis and T regulatory type 1 cells
1 INSERM U430, Institut des Cordeliers, Paris, France 2 Université Paris V René Descartes and Hôpital Européen Georges Pompidou, Paris, France
Correspondence to: L. Weiss; E-mail: laurence.weiss{at}egp.ap-hop-paris.fr
Transmitting editor: M. Feldmann
Dendritic cells (DCs) generated in the presence of IFN-
(IFN-DCs) exhibit high expression of major histocompatibility and co-stimulatory molecules and a potent ability to stimulate CD8+ T-cell responses. Here, we found that IFN-DCs were more potent stimulators of bulk and purified CD8+ T-cell proliferation, as compared with IL-4-DCs. In contrast, IFN-DCs were less efficient than IL-4-DCs in stimulating allogeneic CD4+ T-cell proliferation, due to a weak induction of naive CD4+CD45RO– T-cell proliferation by these DCs. However, both DC populations induced similar levels of proliferation of memory CD4+CD45RO+ T cells. IFN-DCs and IL-4-DCs exhibited a similar phenotype and production of IL-10 following maturation induced by CD40 ligation. In contrast, IFN-DCs produced higher levels of IL-10 during the first days of differentiation. In addition, neutralization of IL-10 during the differentiation of DCs increased the expression of DC-LAMP and MHC class II by IFN-DCs, and the ability of IFN-DCs to stimulate allogeneic CD4+ T-cell proliferation at similar levels, than IL-4-DCs. Independently of IL-10 production, IFN-DCs were found to induce higher levels of CD4+T-cell apoptosis, this effect being more sticking on naive T cells. Finally, we demonstrated that IFN-DCs induced a differentiation bias of naive CD4+ T cells towards Th1 and Tr1 cells, compared to IL-4-DCs. Taken together, these results indicate that, despite the induction of Tr1 cells and enhanced apoptosis of naive CD4+ T cells, IFN-DCs are potent stimulators of CD8+ and memory CD4+ T cells, and induce a strong polarization of naive CD4+ T cells towards Th1 cells, further supporting their use in immune-based therapy.
Keywords: CD4 T cell subsets, cytokines, T lymphocytes
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