Type I interferons (IFNs) are cytokines exhibiting antiviral and antitumor effects, including multiple activities on immune cells. However, the importance of these cytokines in the early events leading to the generation of an immune response is still unclear. Here, we have investigated the effects of type I IFNs on freshly isolated granulocyte/macrophage colony-stimulating factor (GM-CSF)–treated human monocytes in terms of dendritic cell (DC) differentiation and activity in vitro and in severe combined immunodeficiency mice reconstituted with human peripheral blood leukocytes (hu-PBL-SCID) mice. Type I IFNs induced a surprisingly rapid maturation of monocytes into short-lived tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)–expressing DCs endowed with potent functional activities, superior with respect to the interleukin (IL)-4/GM-CSF treatment, as shown by FACS® analyses, mixed leukocyte reaction assays with allogeneic PBLs, and lymphocyte proliferation responses to HIV-1–pulsed autologous DCs. Type I IFN induced IL-15 production and strongly promoted a T helper cell type 1 response. Notably, injection of IFN-treated HIV-1–pulsed DCs in SCID mice reconstituted with autologous PBLs resulted in the generation of a potent primary immune response, as evaluated by the detection of human antibodies to various HIV-1 antigens. These results provide a rationale for using type I IFNs as vaccine adjuvants and support the concept that a natural alliance between these cytokines and monocytes/DCs represents an important early mechanism for connecting innate and adaptive immunity.
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15 May 2000
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May 15 2000
Type I Interferon as a Powerful Adjuvant for Monocyte-Derived Dendritic Cell Development and Activity in Vitro and in Hu-Pbl-Scid Mice
Stefano M. Santini,
Stefano M. Santini
aLaboratory of Virology, Istituto Superiore di Sanità, 00161 Rome, Italy
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Caterina Lapenta,
Caterina Lapenta
aLaboratory of Virology, Istituto Superiore di Sanità, 00161 Rome, Italy
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Mariantonia Logozzi,
Mariantonia Logozzi
aLaboratory of Virology, Istituto Superiore di Sanità, 00161 Rome, Italy
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Stefania Parlato,
Stefania Parlato
aLaboratory of Virology, Istituto Superiore di Sanità, 00161 Rome, Italy
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Massimo Spada,
Massimo Spada
aLaboratory of Virology, Istituto Superiore di Sanità, 00161 Rome, Italy
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Tiziana Di Pucchio,
Tiziana Di Pucchio
aLaboratory of Virology, Istituto Superiore di Sanità, 00161 Rome, Italy
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Filippo Belardelli
Filippo Belardelli
aLaboratory of Virology, Istituto Superiore di Sanità, 00161 Rome, Italy
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Stefano M. Santini
aLaboratory of Virology, Istituto Superiore di Sanità, 00161 Rome, Italy
Caterina Lapenta
aLaboratory of Virology, Istituto Superiore di Sanità, 00161 Rome, Italy
Mariantonia Logozzi
aLaboratory of Virology, Istituto Superiore di Sanità, 00161 Rome, Italy
Stefania Parlato
aLaboratory of Virology, Istituto Superiore di Sanità, 00161 Rome, Italy
Massimo Spada
aLaboratory of Virology, Istituto Superiore di Sanità, 00161 Rome, Italy
Tiziana Di Pucchio
aLaboratory of Virology, Istituto Superiore di Sanità, 00161 Rome, Italy
Filippo Belardelli
aLaboratory of Virology, Istituto Superiore di Sanità, 00161 Rome, Italy
S.M. Santini and C. Lapenta contributed equally to this work.
Abbreviations used in this paper: AT, aldrithiol; CIFN, consensus IFN; DC, dendritic cell; ELISPOT, enzyme-linked immunospot; GFP, green fluorescent protein; hu, human; RT, reverse transcription; s, soluble; TRAIL, TNF-related apoptosis-inducing ligand.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
© 2000 The Rockefeller University Press
2000
The Rockefeller University Press
J Exp Med (2000) 191 (10): 1777–1788.
Citation
Stefano M. Santini, Caterina Lapenta, Mariantonia Logozzi, Stefania Parlato, Massimo Spada, Tiziana Di Pucchio, Filippo Belardelli; Type I Interferon as a Powerful Adjuvant for Monocyte-Derived Dendritic Cell Development and Activity in Vitro and in Hu-Pbl-Scid Mice. J Exp Med 15 May 2000; 191 (10): 1777–1788. doi: https://doi.org/10.1084/jem.191.10.1777
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