PMID- 16297159
OWN - NLM
STAT- MEDLINE
DCOM- 20060113
LR  - 20181203
IS  - 0009-9104 (Print)
IS  - 1365-2249 (Electronic)
IS  - 0009-9104 (Linking)
VI  - 142
IP  - 3
DP  - 2005 Dec
TI  - Interferon-alpha2a is sufficient for promoting dendritic cell immunogenicity.
PG  - 471-80
AB  - Type I interferons (IFNs) are widely used therapeutically. IFN-alpha2a 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-alpha2a on 
      DC maturation and its role in determining Th1/Th2 equilibrium. We found that 
      IFN-alpha2a induced phenotypic maturation of DCs and increased their 
      allostimulatory capacity. When dendritic cells were stimulated simultaneously by 
      CD40 ligation and IFN-alpha2a, the production of interleukin (IL)-10 and IL-12 
      was increased. In contrast, lipopolysaccharide (LPS) stimulation in the presence 
      of IFN-alpha2a 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-alpha2a-treated DCs. Furthermore, IL-12 production by IFN-alpha2a-treated DCs 
      was enhanced further in the presence of anti-IL-10 antibody. Different results 
      were obtained when DCs were treated simultaneously with IFN-alpha2a and other 
      maturation factors, in particular LPS, and then stimulated by CD40 ligation 36 h 
      later. Under these circumstances, IFN-alpha2a 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-alpha2a 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-alpha2a and have direct implications for the design of IFN-alpha-based 
      vaccines for immunotherapy.
FAU - Tamir, A
AU  - Tamir A
AD  - Department of Immunology, Division of Medicine, Faculty of Medicine, Imperial 
      College at Hammersmith Hospital, London, UK.
FAU - Jordan, W J
AU  - Jordan WJ
FAU - Ritter, M
AU  - Ritter M
FAU - Habib, N
AU  - Habib N
FAU - Lechler, R I
AU  - Lechler RI
FAU - Foster, G R
AU  - Foster GR
FAU - Lombardi, G
AU  - Lombardi G
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Clin Exp Immunol
JT  - Clinical and experimental immunology
JID - 0057202
RN  - 0 (Antiviral Agents)
RN  - 0 (CD40 Antigens)
RN  - 0 (Interferon alpha-2)
RN  - 0 (Interferon-alpha)
RN  - 0 (Interleukin-5)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Recombinant Proteins)
RN  - 130068-27-8 (Interleukin-10)
RN  - 187348-17-0 (Interleukin-12)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Antiviral Agents/*immunology
MH  - CD40 Antigens/immunology
MH  - Cell Line
MH  - Dendritic Cells/*immunology
MH  - Enzyme-Linked Immunosorbent Assay/methods
MH  - Interferon alpha-2
MH  - Interferon-alpha/*immunology
MH  - Interferon-gamma/immunology
MH  - Interleukin-10/immunology
MH  - Interleukin-12/immunology
MH  - Interleukin-5/immunology
MH  - Lipopolysaccharides/immunology
MH  - Mice
MH  - Phenotype
MH  - Recombinant Proteins
MH  - Th1 Cells/immunology
MH  - Th2 Cells/immunology
PMC - PMC1809533
EDAT- 2005/11/22 09:00
MHDA- 2006/01/18 09:00
PMCR- 2006/12/01
CRDT- 2005/11/22 09:00
PHST- 2005/11/22 09:00 [pubmed]
PHST- 2006/01/18 09:00 [medline]
PHST- 2005/11/22 09:00 [entrez]
PHST- 2006/12/01 00:00 [pmc-release]
AID - CEI2933 [pii]
AID - 10.1111/j.1365-2249.2005.02933.x [doi]
PST - ppublish
SO  - Clin Exp Immunol. 2005 Dec;142(3):471-80. doi: 10.1111/j.1365-2249.2005.02933.x.