Type I interferon as a powerful adjuvant for monocyte-derived dendritic cell development and activity in vitro and in Hu-PBL-SCID mice.
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((R)) 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.
Santini
S M
SM
Laboratory of Virology, Istituto Superiore di Sanità, 00161 Rome, Italy.
Lapenta
C
C
Logozzi
M
M
Parlato
S
S
Spada
M
M
Di Pucchio
T
T
Belardelli
F
F
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects; D016207:Cytokines / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D015870:Gene Expression / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D015483:HIV Antibodies / Q000096:biosynthesis; D015488:HIV Antigens / Q000235:genetics; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D007370:Interferon Type I / Q000494:pharmacology*; D017708:Leukocyte Transfusion; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D016513:Mice, SCID; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D011994:Recombinant Proteins; D014183:Transplantation, Heterologous
D000276:Adjuvants, Immunologic; D016207:Cytokines; D017931:DNA Primers; D015483:HIV Antibodies; D015488:HIV Antigens; D007370:Interferon Type I; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor