Type I Interferon as a Powerful Adjuvant for Monocyte-Derived Dendritic Cell Development and Activity in Vitro and in Hu-Pbl-Scid Mice
By S. Santini, C. Lapenta, M. Logozzi, S. Parlato, M. Spada, T. Di Pucchio, F. Belardelli. Journal of Experimental Medicine, 2000
734 citations recorded by the source corpus.
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.
Subfields: Immunology
View Paper: https://www.semanticscholar.org/paper/93827ba62a683ea084f378496b9052fa9f23f543
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Citations in the corpus
- Self-RNA–antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8 (2009, background): “Because type I IFNs have been reported to directly stimulate mDCs (Luft et al., 1998; Santini et al., 2000), we next investigated whether pDC-derived type I IFNs could enhance the activation and maturation of mDCs stimulated by self-RNA–LL37 complexes.”
- Functional classification of interferon‐stimulated genes identified using microarrays (2001, background): “IFNs also facilitate the activation immune effector cells [1, 43].”
- Inflammatory signals in dendritic cell activation and the induction of adaptive immunity (2009, background): “A trivial explanation for those findings could be the presence of residual TLR5-expressing hematopoietic cells in the chimeric animals, which act as APCs and contribute DC-activating signals (see below).”
- Interleukins 1β and 6 but not transforming growth factor-β are essential for the differentiation of interleukin 17–producing human T helper cells (2007, methodology): “DCs were obtained from monocytes after culture with granulocyte-macrophage colony-stimulating factor and IL-4, TGF-β or IFN-α as reported befor”
- Type i interferons potently enhance humoral immunity and can promote isotype switching by stimulating dendritic cells in vivo. (2001, background): “However, since 1998), raising the theoretical possibility that the produc- recent studies have shown that IFN-I can promote the tion of antibodies detected 6 months after injection with maturation of human (Luft et al., 1998; Paquette et al., CGG 1 IFN-a/b could have persisted in the absence of 1998”
- Plasmacytoid dendritic cells: sensing nucleic acids in viral infection and autoimmune diseases (2008, background): “Type I IFNs derived from pDCs have been shown to trigger IL-12, IL-15, IL-18 and IL-23 production by mDCs, and to induce monocytes to differentiate into DC”