PMID- 10544185
OWN - NLM
STAT- MEDLINE
DCOM- 19991118
LR  - 20190516
IS  - 0892-6638 (Print)
IS  - 0892-6638 (Linking)
VI  - 13
IP  - 14
DP  - 1999 Nov
TI  - Cycling of human dendritic cell effector phenotypes in response to TNF-alpha: 
      modification of the current 'maturation' paradigm and implications for in vivo 
      immunoregulation.
PG  - 2021-30
AB  - Dendritic cells (DCs) are potent antigen presenting cells reported to undergo 
      irreversible functional 'maturation' in response to inflammatory signals such as 
      TNF-alpha. The current paradigm holds that this DC maturation event is required 
      for full functional capacity and represents terminal differentiation of this cell 
      type, culminating in apoptotic cell death. This provides a possible mechanism for 
      avoiding dysregulated immunostimulatory activity, but imposes constraints on the 
      capacity of DCs to influence subsequent immune responses and to participate in 
      immunological memory. We report that the cell surface and functional effects 
      induced by TNF-alpha are reversible and reinducible. These effects are 
      accompanied by a concordant modulation of cytokine mRNA expression that includes 
      the induction of proinflammatory factors (IL-15, IL-12, LT-alpha, LT-beta, 
      TNF-alpha, RANTES) which is coincident with the down-regulation of 
      counter-regulatory cytokines (IL-10, TGF-beta1, TGF-beta2, IL-1 RA, MCP-1). The 
      resultant net effect is a dendritic cell activation state characterized by a 
      transient proinflammatory posture. These results demonstrate that 1) human DCs do 
      not undergo terminal 'maturation' in response to TNF-alpha, 2) DC phenotypes are 
      more pleiotropic than previously thought, and 3) DCs are potential 
      immunoregulatory effector cells with implications for control of immune responses 
      in both in vivo and in vitro systems.
FAU - Nelson, E L
AU  - Nelson EL
AD  - Immunotherapy Laboratory and Clinical Support Laboratory, National Cancer 
      Institute-Frederick Cancer Research and Development Center, Division of Clinical 
      Sciences, SAIC-Frederick, Frederick, Maryland 21702, USA. 
      enelson@mail.ncifcrf.gov
FAU - Strobl, S
AU  - Strobl S
FAU - Subleski, J
AU  - Subleski J
FAU - Prieto, D
AU  - Prieto D
FAU - Kopp, W C
AU  - Kopp WC
FAU - Nelson, P J
AU  - Nelson PJ
LA  - eng
GR  - N01-CO-56000/CO/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Antigens, CD)
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Antigens, CD/analysis
MH  - Chemokines/genetics
MH  - Cytokines/genetics
MH  - Dendritic Cells/*drug effects/physiology
MH  - Humans
MH  - Monocytes/physiology
MH  - Phenotype
MH  - RNA, Messenger/analysis
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 1999/11/02 00:00
MHDA- 1999/11/02 00:01
CRDT- 1999/11/02 00:00
PHST- 1999/11/02 00:00 [pubmed]
PHST- 1999/11/02 00:01 [medline]
PHST- 1999/11/02 00:00 [entrez]
AID - 10.1096/fasebj.13.14.2021 [doi]
PST - ppublish
SO  - FASEB J. 1999 Nov;13(14):2021-30. doi: 10.1096/fasebj.13.14.2021.