PMID- 12885938
OWN - NLM
STAT- MEDLINE
DCOM- 20030909
LR  - 20190605
IS  - 0741-5400 (Print)
IS  - 0741-5400 (Linking)
VI  - 74
IP  - 2
DP  - 2003 Aug
TI  - Analysis of the maturation process of dendritic cells deficient for TNF and 
      lymphotoxin-alpha reveals an essential role for TNF.
PG  - 216-22
AB  - Dendritic cells (DCs) generated from bone marrow (BM) precursor cells of C57BL/6 
      (B6.WT) mice and cultured in the presence of granulocyte macrophage-colony 
      stimulating factor differentiate to mature BM-DCs spontaneously. These mature DCs 
      are characterized by high levels of major histocompatibility complex (MHC) class 
      II, CD40, and CD86 on their surface. To analyze the involvement of tumor necrosis 
      factor (TNF) and the related cytokine lymphotoxin (LT)alpha in DC maturation, we 
      studied the development of DCs from the BM of B6.TNF(-/-), B6.LTalpha(-/-), and 
      B6.TNF/LTalpha(-/-) mice and compared it to B6.WT mice. Although the development 
      of BM precursor cells to the level of immature DCs (CD11c(+), MHC class II(low), 
      CD40(low), and CD86(low)) was equivalent in all genotypes, B6.TNF(-/-) and 
      B6.TNF/LTalpha(-/-) cells showed an impaired capacity to differentiate to mature 
      DCs. In contrast, mature BM-DCs generated from LTalpha-negative, immature DCs 
      developed like B6.WT cells. Further studies revealed that once matured, the 
      phenotype of all tested genotypes was comparable. They expressed high levels of 
      CD40 and CD86, were exclusively positive for the chemokine receptor (CCR)7 but 
      negative for CCR5 and CCR2, and were able to enter the paracortex of draining 
      lymph nodes. The limited maturation of TNF-deficient BM-DCs could be restored by 
      mixing TNF-negative with TNF-positive Ly5.1 BM cells, and maturation of B6.WT DCs 
      could be blocked with an anti-TNF monoclonal antibody. The substitution of 
      B6.TNF(-/-) BM cells with recombinant TNF revealed promotion or suppression of 
      BM-DC maturation depending on the point of time of TNF addition.
FAU - Ritter, Uwe
AU  - Ritter U
AD  - Nikolaus-Fiebiger Zentrum fur Molekulare Medizin, Erlangen, Germany. 
      hkoerner@molmed.uni-erlangen.de
FAU - Meissner, Anja
AU  - Meissner A
FAU - Ott, Jessica
AU  - Ott J
FAU - Korner, Heinrich
AU  - Korner H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (Antigens, CD)
RN  - 0 (B7-2 Antigen)
RN  - 0 (CD40 Antigens)
RN  - 0 (Ccr7 protein, mouse)
RN  - 0 (Cd86 protein, mouse)
RN  - 0 (Lymphotoxin-alpha)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Receptors, CCR7)
RN  - 0 (Receptors, Chemokine)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
SB  - IM
MH  - Animals
MH  - Antigens, CD/metabolism
MH  - B7-2 Antigen
MH  - Bone Marrow Cells/cytology
MH  - CD40 Antigens/metabolism
MH  - Cell Differentiation
MH  - Cell Division
MH  - Cells, Cultured
MH  - Dendritic Cells/*cytology/metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Flow Cytometry
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/metabolism
MH  - Lymph Nodes/metabolism
MH  - Lymphotoxin-alpha/deficiency/*physiology
MH  - Membrane Glycoproteins/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Receptors, CCR7
MH  - Receptors, Chemokine/metabolism/physiology
MH  - Recombinant Proteins/pharmacology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tumor Necrosis Factor-alpha/deficiency/*physiology
EDAT- 2003/07/30 05:00
MHDA- 2003/09/10 05:00
CRDT- 2003/07/30 05:00
PHST- 2003/07/30 05:00 [pubmed]
PHST- 2003/09/10 05:00 [medline]
PHST- 2003/07/30 05:00 [entrez]
AID - 10.1189/jlb.1202587 [doi]
PST - ppublish
SO  - J Leukoc Biol. 2003 Aug;74(2):216-22. doi: 10.1189/jlb.1202587.