PMID- 20560799
OWN - NLM
STAT- MEDLINE
DCOM- 20101116
LR  - 20100715
IS  - 1744-7631 (Electronic)
IS  - 1472-8222 (Linking)
VI  - 14
IP  - 8
DP  - 2010 Aug
TI  - Induction of pathogenic cytotoxic T lymphocyte tolerance by dendritic cells: a 
      novel therapeutic target.
PG  - 797-824
LID - 10.1517/14728222.2010.499360 [doi]
AB  - IMPORTANCE OF THE FIELD: Dendritic cells (DCs) have an important role, both 
      direct and indirect, in controlling the expansion and function of T cells. Of the 
      different subsets of T cells, cytotoxic T lymphocytes (CTLs/CD8(+) T cells) have 
      been implicated in the pathogenesis and development of many diseases, including 
      various forms of autoimmunity and transplant rejection. It may therefore be of 
      therapeutic benefit to control the function of CTL in order to modulate disease 
      processes and to ameliorate disease symptoms. Currently, pharmacological 
      approaches have been employed to either directly or indirectly modulate the 
      function of T cells. However, these treatment strategies have many limitations. 
      Many experimental data have suggested that it is possible to alter CTL activity 
      through manipulation of DC. AREAS COVERED IN THIS REVIEW: Novel strategies that 
      condition DCs to influence disease outcome through manipulation of CTL activity, 
      both directly and indirectly. This includes the modulation of co-stimulation, 
      negative co-stimulation, as well as manipulation of the cytokine milieu during 
      CTL generation. Furthermore, DCs may also impact CTL activity through effects on 
      effector and regulatory cells, along with manipulation of bioenergetic 
      regulation, apoptotic-cell mediated tolerance and through the generation of 
      exosomes. The implications of related interventions in the clinical arena are in 
      turn considered. WHAT THE READER WILL GAIN: Insight into such indirect methods of 
      controlling CTL activity allows for an understanding of how disease-specific T 
      cells may be regulated, while also sparing other aspects of adaptive immunity for 
      normal physiological function. Such an approach towards the treatment of disease 
      represents an innovative therapeutic target in the clinical arena. TAKE HOME 
      MESSAGE: There are numerous innovative methods for using DCs to control CTL 
      responses. Manipulation of this interaction is thus an attractive avenue for the 
      treatment of disease, particularly those of immune dysregulation, such as seen in 
      autoimmunity and transplantation. With the number of studies moving into clinical 
      stages constantly increasing, further advances and successes in this area are 
      inevitable.
FAU - Gill, Dipender
AU  - Gill D
AD  - University of Oxford, John Radcliffe Hospital, Nuffield Department of Surgery, 
      Headley Way, Oxford, OX3 9DU, UK.
FAU - Tan, Peng H
AU  - Tan PH
LA  - eng
PT  - Journal Article
PT  - Review
PL  - England
TA  - Expert Opin Ther Targets
JT  - Expert opinion on therapeutic targets
JID - 101127833
SB  - IM
MH  - *Adaptive Immunity
MH  - Animals
MH  - Apoptosis
MH  - Dendritic Cells/*immunology/metabolism
MH  - Exosomes/immunology/physiology
MH  - Humans
MH  - Immune Tolerance
MH  - Lymphocyte Activation
MH  - Mice
MH  - Rats
MH  - Signal Transduction
MH  - T-Lymphocytes, Cytotoxic/*immunology/metabolism
EDAT- 2010/06/22 06:00
MHDA- 2010/11/17 06:00
CRDT- 2010/06/22 06:00
PHST- 2010/06/22 06:00 [entrez]
PHST- 2010/06/22 06:00 [pubmed]
PHST- 2010/11/17 06:00 [medline]
AID - 10.1517/14728222.2010.499360 [doi]
PST - ppublish
SO  - Expert Opin Ther Targets. 2010 Aug;14(8):797-824. doi: 
      10.1517/14728222.2010.499360.