TY - JOUR
T1 - Interferon-alpha 2a is sufficient for promoting dendritic cell immunogenicity
AU - Tamir, A
AU - Jordan, W J
AU - Ritter, M
AU - Habib, N
AU - Lechler, R I
AU - Foster, G R
AU - Lombardi, G
PY - 2005/12
Y1 - 2005/12
N2 - Type I interferons (IFNs) are widely used therapeutically. IFN-alpha 2a in particular is used as an antiviral agent, but its immunomodulatory properties are poorly understood. Dendritic cells (DCs) are the only antigen-presenting cells able to prime naive T cells and therefore play a crucial role in initiating the adaptive phase of the immune response. We studied the effects of IFN-alpha 2a on DC maturation and its role in determining Th1/Th2 equilibrium. We found that IFN-alpha 2a induced phenotypic maturation of DCs and increased their allo-stimulatory capacity. When dendritic cells were stimulated simultaneously by CD40 ligation and IFN-alpha 2a, the production of interleukin (IL)-10 and IL-12 was increased. In contrast, lipopolysaccharide (LPS) stimulation in the presence of IFN-alpha 2a mainly induced IL-10 release. The production of IFN-gamma and IL-5 by the responder naive T cells was also amplified in response to IFN-alpha 2a-treated DCs. Furthermore, IL-12 production by IFN-alpha 2a-treated DCs was enhanced further in the presence of anti-IL-10 antibody. Different results were obtained when DCs were treated simultaneously with IFN-alpha 2a and other maturation factors, in particular LPS, and then stimulated by CD40 ligation 36 h later. Under these circumstances, IFN-alpha 2a did not modify the DC phenotype, and the production of IL-10/IL-12 and IFN-gamma/IL-5 by DCs and by DC-stimulated naive T cells, respectively, was inhibited compared to the effects on DCs treated with maturation factors alone. Altogether, this work suggests that IFN-alpha 2a in isolation is sufficient to promote DC activation, however, other concomitant events, such as exposure to LPS during a bacterial infection, can inhibit its effects. These results clarify some of the in vivo findings obtained with IFN-alpha 2a and have direct implications for the design of IFN-alpha-based vaccines for immunotherapy
AB - Type I interferons (IFNs) are widely used therapeutically. IFN-alpha 2a in particular is used as an antiviral agent, but its immunomodulatory properties are poorly understood. Dendritic cells (DCs) are the only antigen-presenting cells able to prime naive T cells and therefore play a crucial role in initiating the adaptive phase of the immune response. We studied the effects of IFN-alpha 2a on DC maturation and its role in determining Th1/Th2 equilibrium. We found that IFN-alpha 2a induced phenotypic maturation of DCs and increased their allo-stimulatory capacity. When dendritic cells were stimulated simultaneously by CD40 ligation and IFN-alpha 2a, the production of interleukin (IL)-10 and IL-12 was increased. In contrast, lipopolysaccharide (LPS) stimulation in the presence of IFN-alpha 2a mainly induced IL-10 release. The production of IFN-gamma and IL-5 by the responder naive T cells was also amplified in response to IFN-alpha 2a-treated DCs. Furthermore, IL-12 production by IFN-alpha 2a-treated DCs was enhanced further in the presence of anti-IL-10 antibody. Different results were obtained when DCs were treated simultaneously with IFN-alpha 2a and other maturation factors, in particular LPS, and then stimulated by CD40 ligation 36 h later. Under these circumstances, IFN-alpha 2a did not modify the DC phenotype, and the production of IL-10/IL-12 and IFN-gamma/IL-5 by DCs and by DC-stimulated naive T cells, respectively, was inhibited compared to the effects on DCs treated with maturation factors alone. Altogether, this work suggests that IFN-alpha 2a in isolation is sufficient to promote DC activation, however, other concomitant events, such as exposure to LPS during a bacterial infection, can inhibit its effects. These results clarify some of the in vivo findings obtained with IFN-alpha 2a and have direct implications for the design of IFN-alpha-based vaccines for immunotherapy
U2 - 10.1111/j.1365-2249.2005.02933.x
DO - 10.1111/j.1365-2249.2005.02933.x
M3 - Article
SN - 1365-2249
VL - 142
SP - 471
EP - 480
JO - Clinical and Experimental Immunology
JF - Clinical and Experimental Immunology
IS - 3
ER -