PMID- 12351809
OWN - NLM
STAT- MEDLINE
DCOM- 20030312
LR  - 20181130
IS  - 1066-5099 (Print)
IS  - 1066-5099 (Linking)
VI  - 20
IP  - 5
DP  - 2002
TI  - Differentiation of immunostimulatory stem-cell- and monocyte-derived dendritic 
      cells involves maturation of intracellular compartments responsible for antigen 
      presentation and secretion.
PG  - 380-93
AB  - Dendritic cells (DCs) are important for the induction of primary T-cell responses 
      and may serve as "biologic adjuvants" in therapeutic protocols. However, given 
      the "plasticity" of this antigen-presenting cell, it remains unclear which DC 
      type (source, subtype, and stage of differentiation) should be applied 
      clinically. To provide additional insight in this selection process, we have, for 
      the first time, analyzed the in vitro differentiation of CD34(+) 
      precursor-derived and monocyte-derived DCs for ultrastructure, phenotype, and 
      function. The ultrastructural intracytoplasmic differentiation of DCs correlated 
      with increasing T-cell stimulatory activity of these cells. "Early-stage"-DCs 
      proliferate, exhibit high levels of soluble antigen uptake, and moderate T-cell 
      stimulatory capacity, and are characterized by centrally located nuclei and 
      numerous enlarged mitochondria. "Intermediate-stage"-DCs are enlarged cells with 
      enhanced T-cell stimulatory activity and pronounced cytoplasmic protein synthesis 
      machinery. "Late-stage" (LS)-DCs exhibit a mature secretory cell phenotype and 
      low proliferative index. They express high levels of the HLA-DR, CD40L, B7-1, and 
      B7-2 molecules and CD83, a specific marker of mature DCs, and appear maximally 
      stimulatory to T cells. Ultrastructurally, LS-DCs feature an accentric nucleus, 
      an enlarged cytoplasm, containing numerous secretory storage vesicles, along with 
      a fully developed Golgi complex. LS-DCs exhibited numerous multivesicular and 
      multilaminar structures containing major histocompatibility complex class II 
      molecules, consistent with the MIIC (peptide-loading) compartment. In extended 
      studies, cultured CD14(+) monocyte-derived DCs displayed a similar, but 
      accelerated, temporal differentiation staging pattern.
FAU - Bykovskaia, Svetlana N
AU  - Bykovskaia SN
AD  - University of Pittsburgh Medical Center, University of Pittsburgh Cancer 
      Institute, Pittsburgh, Pennsylvania 15261, USA. Bykovskaias@exchange.upmc.edu
FAU - Shurin, Galina V
AU  - Shurin GV
FAU - Graner, Scott
AU  - Graner S
FAU - Bunker, Mark L
AU  - Bunker ML
FAU - Olson, Walter
AU  - Olson W
FAU - Thomas, Ronald
AU  - Thomas R
FAU - Shurin, Michael R
AU  - Shurin MR
FAU - Marks, Stanley
AU  - Marks S
FAU - Storkus, Walter J
AU  - Storkus WJ
FAU - Shogan, Jeffrey
AU  - Shogan J
LA  - eng
GR  - CA 73743/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Stem Cells
JT  - Stem cells (Dayton, Ohio)
JID - 9304532
RN  - 0 (Antigens, CD)
RN  - 0 (HLA-DR Antigens)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Antigen Presentation/*immunology
MH  - Antigens, CD/*immunology
MH  - Cell Compartmentation/*immunology
MH  - Cell Differentiation/*immunology
MH  - Cells, Cultured
MH  - Dendritic Cells/*immunology/metabolism/ultrastructure
MH  - Fetal Blood
MH  - HLA-DR Antigens/immunology
MH  - Humans
MH  - Interferon-gamma/metabolism
MH  - Lymphocyte Activation/*immunology
MH  - Microscopy, Electron
MH  - Monocytes/cytology/immunology
MH  - Organelles/*immunology/metabolism/ultrastructure
MH  - Stem Cells/cytology/immunology
MH  - T-Lymphocytes/*immunology
EDAT- 2002/09/28 04:00
MHDA- 2003/03/13 04:00
CRDT- 2002/09/28 04:00
PHST- 2002/09/28 04:00 [pubmed]
PHST- 2003/03/13 04:00 [medline]
PHST- 2002/09/28 04:00 [entrez]
AID - 10.1634/stemcells.20-5-380 [doi]
PST - ppublish
SO  - Stem Cells. 2002;20(5):380-93. doi: 10.1634/stemcells.20-5-380.