PMID- 17949888
OWN - NLM
STAT- MEDLINE
DCOM- 20080304
LR  - 20210103
IS  - 0301-472X (Print)
IS  - 0301-472X (Linking)
VI  - 36
IP  - 1
DP  - 2008 Jan
TI  - Human Flt-3-ligand-mobilized dendritic cells require additional activation to 
      drive effective immune responses.
PG  - 51-60
AB  - OBJECTIVE: Dendritic cells (DCs) play a pivotal role in the induction of immunity 
      in response to pathogenic challenge or vaccination. As such, the fms-like 
      tyrosine kinase 3-ligand (Flt-3L) has been used to increase DC populations in 
      vivo, with contrasting outcomes, which include an increase in immunity, tolerance 
      induction, or expansion of regulatory cells. This study examines the adjuvant 
      role that human Flt-3L (hFL) administration has in generating immune responses 
      upon immunization with a poorly immunogenic and soluble protein antigen. 
      MATERIALS AND METHODS: Mice were immunized with the nominal antigen, ovalbumin, 
      alone or with antigen emulsified in complete Freund's adjuvant (CFA), with or 
      without prior hFL-mediated expansion of DC subsets. The maturation of DC subsets 
      and activation status of antigen-specific T cells were analyzed by flow 
      cytometry, with effector function assessed in cytolytic T-lymphocyte assays. 
      RESULTS: hFL treatment expanded both conventional DC and plasmacytoid DC in vivo, 
      resulting in increased antigen presentation by both direct and cross-presentation 
      pathways. However, it was only in the context of CFA that antigen immunization 
      could mature DCs and subsequently fully activate antigen-specific T cells with 
      enhanced cytolytic activity. CONCLUSIONS: Our studies reveal that hFL essentially 
      acts as a coadjuvant, as hFL augments the size of an immune response but requires 
      further adjuvant activation to alter the quality of the response.
FAU - Diener, Kerrilyn R
AU  - Diener KR
AD  - Hanson Institute, South Australia, Australia.
FAU - Moldenhauer, Lachlan M
AU  - Moldenhauer LM
FAU - Lyons, A Bruce
AU  - Lyons AB
FAU - Brown, Michael P
AU  - Brown MP
FAU - Hayball, John D
AU  - Hayball JD
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071018
PL  - Netherlands
TA  - Exp Hematol
JT  - Experimental hematology
JID - 0402313
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Egg Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (OVA 323-339)
RN  - 0 (OVA-8)
RN  - 0 (Peptide Fragments)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (flt3 ligand protein)
RN  - 9006-59-1 (Ovalbumin)
RN  - 9007-81-2 (Freund's Adjuvant)
SB  - IM
MH  - Adjuvants, Immunologic
MH  - Adoptive Transfer
MH  - Amino Acid Sequence
MH  - Animals
MH  - Antigen Presentation/*drug effects/physiology
MH  - Cytotoxicity, Immunologic/drug effects
MH  - Dendritic Cells/classification/*drug effects/immunology
MH  - Egg Proteins/immunology
MH  - Freund's Adjuvant/pharmacology
MH  - Humans
MH  - Immunization
MH  - Lymph Nodes/cytology/immunology
MH  - Lymphocyte Activation
MH  - Membrane Proteins/immunology/*pharmacology/physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Molecular Sequence Data
MH  - Ovalbumin/immunology
MH  - Peptide Fragments/immunology
MH  - Recombinant Fusion Proteins/pharmacology
MH  - Spleen/cytology/immunology
MH  - T-Lymphocyte Subsets/immunology
EDAT- 2007/10/24 09:00
MHDA- 2008/03/05 09:00
CRDT- 2007/10/24 09:00
PHST- 2007/05/28 00:00 [received]
PHST- 2007/08/02 00:00 [revised]
PHST- 2007/08/20 00:00 [accepted]
PHST- 2007/10/24 09:00 [pubmed]
PHST- 2008/03/05 09:00 [medline]
PHST- 2007/10/24 09:00 [entrez]
AID - S0301-472X(07)00533-4 [pii]
AID - 10.1016/j.exphem.2007.08.024 [doi]
PST - ppublish
SO  - Exp Hematol. 2008 Jan;36(1):51-60. doi: 10.1016/j.exphem.2007.08.024. Epub 2007 
      Oct 18.