PMID- 10498601
OWN - NLM
STAT- MEDLINE
DCOM- 19991104
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 94
IP  - 7
DP  - 1999 Oct 1
TI  - Rapid induction of CD40 on a subset of granulocyte colony-stimulating 
      factor-mobilized CD34(+) blood cells identifies myeloid committed progenitors and 
      permits selection of nonimmunogenic CD40(-) progenitor cells.
PG  - 2293-300
AB  - CD40 antigen is a costimulatory molecule highly expressed on dendritic cells (DC) 
      and activated B cells, which induces T-cell proliferation through the binding 
      with CD40L receptor. In this study, we evaluated CD40 expression on normal 
      CD34(+) blood cells and functionally characterized CD34(+)CD40(+) and 
      CD34(+)CD40(-) cell subsets. CD40, CD80, and CD86 antigens were constitutively 
      expressed on 3.2% +/- 4.5%, 0%, and 1.8% +/- 1.2% CD34(+) blood cells, 
      respectively. However, after 24 hours in liquid culture with medium alone, or 
      with tumor-necrosis-factor-alpha (TNF-alpha), or with allogeneic mononuclear 
      cells 10.8% +/- 3.8%, 75.3% +/- 15.0% and 53. 7% +/- 17.0% CD34(+) blood cells, 
      respectively, became CD40(+). After incubation for 24 hours with TNF-alpha 
      CD34(+)CD40(+) blood cells expressed only myeloid markers and contained less than 
      5% CD86(+) and CD80(+) cells. Also, a 24-hour priming with TNF-alpha or ligation 
      of CD40 significantly increased the CD34(+) blood cells alloantigen presenting 
      function. Finally, purified CD34(+)CD40(+) blood cells stimulated an alloreactive 
      T-cell response in MLC, were enriched in granulocytic, monocytic, and dendritic 
      precursors, and generated high numbers of DC in 11-14 d liquid cultures with 
      GM-CSF, SCF, TNF-alpha and FLT-3L. In contrast, CD34(+)CD40(-) cells were poorly 
      immunogenic, contained committed granulocytic and erythroid precursors and early 
      progenitors, and differentiated poorly toward the DC lineage. In conclusion, a 
      short incubation with TNF-alpha allows the selection of CD40(+) blood 
      progenitors, which may be a useful source of DC precursors for antitumor vaccine 
      studies, and also a CD34(+)CD40(-) blood cell fraction that could be exploited in 
      innovative strategies of allogeneic transplantation across HLA barriers.
FAU - Rondelli, D
AU  - Rondelli D
AD  - Institute of Hematology and Medical Oncology, "Seragnoli," University of Bologna, 
      Bologna, Italy. drond@med.unibo.it
FAU - Lemoli, R M
AU  - Lemoli RM
FAU - Ratta, M
AU  - Ratta M
FAU - Fogli, M
AU  - Fogli M
FAU - Re, F
AU  - Re F
FAU - Curti, A
AU  - Curti A
FAU - Arpinati, M
AU  - Arpinati M
FAU - Tura, S
AU  - Tura S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, CD34)
RN  - 0 (CD40 Antigens)
RN  - 0 (Growth Substances)
RN  - 0 (Membrane Proteins)
RN  - 0 (Stem Cell Factor)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (flt3 ligand protein)
RN  - 143011-72-7 (Granulocyte Colony-Stimulating Factor)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
SB  - IM
MH  - Adult
MH  - Antigens, CD/biosynthesis/*blood
MH  - Antigens, CD34/*blood
MH  - CD40 Antigens/biosynthesis/*blood
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Colony-Forming Units Assay
MH  - Erythroid Precursor Cells/cytology
MH  - Granulocyte Colony-Stimulating Factor/*pharmacology
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology
MH  - Granulocytes/cytology
MH  - Growth Substances/*pharmacology
MH  - Hematopoietic Stem Cell Mobilization/methods
MH  - Hematopoietic Stem Cells/*cytology/*physiology
MH  - Humans
MH  - Kinetics
MH  - Leukocytes, Mononuclear/cytology/physiology
MH  - Lymphocyte Activation
MH  - Lymphocyte Culture Test, Mixed
MH  - Membrane Proteins/pharmacology
MH  - Stem Cell Factor/pharmacology
MH  - T-Lymphocytes/*immunology
MH  - Tumor Necrosis Factor-alpha/pharmacology
EDAT- 1999/09/25 00:00
MHDA- 1999/09/25 00:01
CRDT- 1999/09/25 00:00
PHST- 1999/09/25 00:00 [pubmed]
PHST- 1999/09/25 00:01 [medline]
PHST- 1999/09/25 00:00 [entrez]
AID - S0006-4971(20)71122-5 [pii]
PST - ppublish
SO  - Blood. 1999 Oct 1;94(7):2293-300.