PMID- 11823490
OWN - NLM
STAT- MEDLINE
DCOM- 20020304
LR  - 20220227
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 168
IP  - 4
DP  - 2002 Feb 15
TI  - Inhibitory effects of apoptotic cell ingestion upon endotoxin-driven myeloid 
      dendritic cell maturation.
PG  - 1627-35
AB  - Dendritic cells (DCs) are the sentinels of the immune system, able to interact 
      with both naive and memory T cells. The recent observation that DCs can ingest 
      cells dying by apoptosis has raised the possibility that DCs may, in fact, 
      present self-derived Ags, initiating both autoimmunity and tumor-specific 
      responses, especially if associated with appropriate danger signals. Although the 
      process of ingestion of apoptotic cells has not been shown to induce DC 
      maturation, the exact fate of these phagocytosing DCs remains unclear. In this 
      paper we demonstrate that DCs that ingest apoptotic cells are able to produce 
      TNF-alpha but have a diminished ability to produce IL-12 in response to external 
      stimuli, a property that corresponds to a failure to up-regulate CD86. By 
      single-cell analysis we demonstrate that these inhibitory effects are restricted 
      to those DCs that have engulfed apoptotic cells, with bystander DCs remaining 
      unaffected. These changes were independent of the production of anti-inflammatory 
      cytokines TGF-beta1 and IL-10 and corresponded with a diminished capacity to 
      stimulate naive T cells. Thus, the ingestion of apoptotic cells is not an 
      immunologically null event but is capable of modulating DC maturation. These 
      results have important implications for our understanding of the role of 
      clearance of dying cells by DCs not only in the normal resolution of inflammation 
      but also in control of subsequent immune responses to apoptotic cell-derived Ags.
FAU - Stuart, Lynda M
AU  - Stuart LM
AD  - Medical Research Council Center for Inflammation Research, University of 
      Edinburgh, Edinburgh, Scotland, United Kingdom. lynda.stuart@ed.ac.uk
FAU - Lucas, Mark
AU  - Lucas M
FAU - Simpson, Cathy
AU  - Simpson C
FAU - Lamb, Jonathan
AU  - Lamb J
FAU - Savill, John
AU  - Savill J
FAU - Lacy-Hulbert, Adam
AU  - Lacy-Hulbert A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Antigens, CD)
RN  - 0 (B7-2 Antigen)
RN  - 0 (Cd86 protein, mouse)
RN  - 0 (Cytokines)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Tgfb1 protein, mouse)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
MH  - Animals
MH  - Antigens, CD/metabolism
MH  - *Apoptosis
MH  - B7-2 Antigen
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Cytokines/biosynthesis
MH  - Dendritic Cells/drug effects/*immunology
MH  - Interleukin-10/genetics/physiology
MH  - Lipopolysaccharides/*pharmacology
MH  - Lymphocyte Activation
MH  - Membrane Glycoproteins/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Knockout
MH  - Myeloid Progenitor Cells/*immunology
MH  - Phagocytosis
MH  - T-Lymphocytes/immunology
MH  - Transforming Growth Factor beta/physiology
MH  - Transforming Growth Factor beta1
MH  - Up-Regulation
EDAT- 2002/02/02 10:00
MHDA- 2002/03/05 10:01
CRDT- 2002/02/02 10:00
PHST- 2002/02/02 10:00 [pubmed]
PHST- 2002/03/05 10:01 [medline]
PHST- 2002/02/02 10:00 [entrez]
AID - 10.4049/jimmunol.168.4.1627 [doi]
PST - ppublish
SO  - J Immunol. 2002 Feb 15;168(4):1627-35. doi: 10.4049/jimmunol.168.4.1627.