PMID- 15184347 OWN - NLM STAT- MEDLINE DCOM- 20050126 LR - 20171116 IS - 0953-8178 (Print) IS - 0953-8178 (Linking) VI - 16 IP - 7 DP - 2004 Jul TI - Dendritic cells generated in the presence of interferon-alpha stimulate allogeneic CD4+ T-cell proliferation: modulation by autocrine IL-10, enhanced T-cell apoptosis and T regulatory type 1 cells. PG - 1037-52 AB - Dendritic cells (DCs) generated in the presence of IFN-alpha (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. FAU - Carbonneil, Cedric AU - Carbonneil C AD - INSERM U430, Institut des Cordeliers, Paris, France. FAU - Saidi, Hela AU - Saidi H FAU - Donkova-Petrini, Vladimira AU - Donkova-Petrini V FAU - Weiss, Laurence AU - Weiss L LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20040607 PL - England TA - Int Immunol JT - International immunology JID - 8916182 RN - 0 (CD40 Antigens) RN - 0 (Interferon-alpha) RN - 130068-27-8 (Interleukin-10) RN - 207137-56-2 (Interleukin-4) RN - EC 3.1.3.48 (Leukocyte Common Antigens) RN - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 1) SB - IM MH - Apoptosis/*immunology MH - CD4-Positive T-Lymphocytes/cytology/*immunology MH - CD40 Antigens/immunology MH - CD8-Positive T-Lymphocytes/immunology MH - Cell Division/*immunology MH - Cells, Cultured MH - Dendritic Cells/*immunology MH - Humans MH - Immunologic Memory/immunology MH - Interferon-alpha/*immunology MH - Interleukin-10/*immunology MH - Interleukin-4/immunology MH - Leukocyte Common Antigens/immunology MH - Protein Tyrosine Phosphatase, Non-Receptor Type 1 MH - Th1 Cells/immunology EDAT- 2004/06/09 05:00 MHDA- 2005/01/27 09:00 CRDT- 2004/06/09 05:00 PHST- 2004/06/09 05:00 [pubmed] PHST- 2005/01/27 09:00 [medline] PHST- 2004/06/09 05:00 [entrez] AID - dxh106 [pii] AID - 10.1093/intimm/dxh106 [doi] PST - ppublish SO - Int Immunol. 2004 Jul;16(7):1037-52. doi: 10.1093/intimm/dxh106. Epub 2004 Jun 7.