PMID- 19941109
OWN - NLM
STAT- MEDLINE
DCOM- 20100202
LR  - 20131121
IS  - 1940-6029 (Electronic)
IS  - 1064-3745 (Linking)
VI  - 595
DP  - 2010
TI  - Pharmacological modification of dendritic cells to promote their tolerogenicity 
      in transplantation.
PG  - 135-48
LID - 10.1007/978-1-60761-421-0_8 [doi]
AB  - Dendritic cells (DCs) are uniquely specialized antigen-presenting cells (APC) 
      that play critical roles in both the stimulation and regulation of immune 
      responses, including T-cell responses to transplanted organs. The inherent 
      tolerogenicity of non-activated or "immature" DCs is well documented. 
      Importantly, the infusion of DCs that are made resistant to activating 
      inflammatory stimuli by "conditioning" through exposure to clinically approved 
      immunosuppressants, such as corticosteroids, deoxyspergualin, and recently, 
      rapamycin (RAPA), has produced encouraging outcomes in experimental models. 
      Indeed, the infusion of RAPA-conditioned, host-derived DCs, pulsed with 
      alloantigen, prolongs allograft survival. In particular, when the 
      RAPA-conditioned DCs are delivered repeatedly or in combination with a short 
      course of immunosuppression indefinite allograft survival is observed, typically 
      associated with increased Foxp3(+) T-regulatory cells (Treg). Herein, we detail 
      the procedures to generate and characterize RAPA-conditioned murine DCs 
      (RAPA-DCs) ex vivo and in vivo. RAPA-DCs represent a pharmacologically 
      conditioned DC population that promotes allograft survival and enriches for 
      antigen-specific T-regulatory cells (Treg). DCs conditioned with 
      immunosuppressive agents, like RAPA, represent novel and clinically applicable 
      vectors or "negative" cellular vaccines, which can be loaded with donor antigen, 
      and potentially used to promote/maintain organ transplant tolerance.
FAU - Turnquist, Hth R
AU  - Turnquist HR
AD  - Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, 
      PA, USA.
FAU - Fischer, Ryan T
AU  - Fischer RT
FAU - Thomson, Angus W
AU  - Thomson AW
LA  - eng
GR  - F32AI072940/AI/NIAID NIH HHS/United States
GR  - R01AI41011/AI/NIAID NIH HHS/United States
GR  - R01AI60994/AI/NIAID NIH HHS/United States
GR  - T32 DK71492/DK/NIDDK NIH HHS/United States
GR  - T32CA082084/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Methods Mol Biol
JT  - Methods in molecular biology (Clifton, N.J.)
JID - 9214969
RN  - 0 (Immunosuppressive Agents)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Dendritic Cells/*drug effects/immunology/*transplantation
MH  - Flow Cytometry
MH  - Immunosuppressive Agents/*pharmacology
MH  - Mice
MH  - Sirolimus/*pharmacology
MH  - Transplantation Tolerance/*drug effects/immunology
EDAT- 2009/11/27 06:00
MHDA- 2010/02/03 06:00
CRDT- 2009/11/27 06:00
PHST- 2009/11/27 06:00 [entrez]
PHST- 2009/11/27 06:00 [pubmed]
PHST- 2010/02/03 06:00 [medline]
AID - 10.1007/978-1-60761-421-0_8 [doi]
PST - ppublish
SO  - Methods Mol Biol. 2010;595:135-48. doi: 10.1007/978-1-60761-421-0_8.