PMID- 22500950
OWN - NLM
STAT- MEDLINE
DCOM- 20121012
LR  - 20230124
IS  - 1600-6143 (Electronic)
IS  - 1600-6135 (Print)
IS  - 1600-6135 (Linking)
VI  - 12
IP  - 6
DP  - 2012 Jun
TI  - Dendritic cell therapies in transplantation revisited: deletion of recipient DCs 
      deters the effect of therapeutic DCs.
PG  - 1398-408
LID - 10.1111/j.1600-6143.2012.04060.x [doi]
AB  - A critical goal in transplantation is the achievement of donor-specific 
      tolerance, minimizing the use of immunosuppressants. Dendritic cells (DCs) are 
      antigen (Ag) presenting cells (APCs) with capability to promote immunity or 
      tolerance. The immune-regulatory properties of DCs have been exploited for 
      generation of tolerogenic/immunosuppressive (IS) DCs that, when transfer 
      systemically, prolong allograft survival in murine models. Surprisingly, the in 
      vivo mechanisms of therapies based on (donor- or recipient-derived) ISDCs in 
      transplantation remain unknown, given that previous studies investigated their 
      effects in vitro, or ex vivo after transplantation. Since once injected, ISDCs 
      are short-lived and transfer Ag to recipient APCs, we assessed the role of 
      recipient DCs by depleting them at the time of ISDC-therapy in a mouse model of 
      cardiac transplantation. The results indicate that, contrary to the accepted 
      paradigm, systemically administered ISDCs reduce the alloresponse and prolong 
      allograft survival, not by themselves, but through conventional DCs (cDCs) of the 
      recipient. These findings raise doubts on the advantages of the currently used 
      ISDC-therapies, since the immune-regulatory properties of the injected ISDC do 
      not seem to be functionally relevant in vivo, and the quiescent/pro-tolerogenic 
      status of cDCs may be compromised in patients with end-stage diseases that 
      require transplantation.
CI  - (c) Copyright 2012 The American Society of Transplantation and the American Society 
      of Transplant Surgeons.
FAU - Wang, Z
AU  - Wang Z
AD  - T. E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, 
      USA.
FAU - Divito, S J
AU  - Divito SJ
FAU - Shufesky, W J
AU  - Shufesky WJ
FAU - Sumpter, T
AU  - Sumpter T
FAU - Wang, H
AU  - Wang H
FAU - Tkacheva, O A
AU  - Tkacheva OA
FAU - Wang, W
AU  - Wang W
FAU - Liu, C
AU  - Liu C
FAU - Larregina, A T
AU  - Larregina AT
FAU - Morelli, A E
AU  - Morelli AE
LA  - eng
GR  - R01 AI077511/AI/NIAID NIH HHS/United States
GR  - R01 HL077545-01A1/HL/NHLBI NIH HHS/United States
GR  - F30 DK082131-01/DK/NIDDK NIH HHS/United States
GR  - R01 HL077545-02/HL/NHLBI NIH HHS/United States
GR  - R01 AI077511-02/AI/NIAID NIH HHS/United States
GR  - R01 HL077545/HL/NHLBI NIH HHS/United States
GR  - F30 DK082131/DK/NIDDK NIH HHS/United States
GR  - R01 HL077545-04/HL/NHLBI NIH HHS/United States
GR  - R01 HL077545-03/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120414
PL  - United States
TA  - Am J Transplant
JT  - American journal of transplantation : official journal of the American Society of 
      Transplantation and the American Society of Transplant Surgeons
JID - 100968638
RN  - 0 (Immunosuppressive Agents)
SB  - IM
CIN - Am J Transplant. 2012 Jun;12(6):1363-4. PMID: 22642470
MH  - Adoptive Transfer
MH  - Animals
MH  - *Dendritic Cells
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Flow Cytometry
MH  - Immunosuppressive Agents/administration & dosage
MH  - Mice
MH  - Mice, Inbred Strains
MH  - *Transplantation
PMC - PMC3365643
MID - NIHMS364017
COIS- Disclosure The authors of this manuscript have no conflict of interest to 
      disclose as described by the American Journal of Transplantation
EDAT- 2012/04/17 06:00
MHDA- 2012/10/13 06:00
PMCR- 2013/06/01
CRDT- 2012/04/17 06:00
PHST- 2012/04/17 06:00 [entrez]
PHST- 2012/04/17 06:00 [pubmed]
PHST- 2012/10/13 06:00 [medline]
PHST- 2013/06/01 00:00 [pmc-release]
AID - S1600-6135(22)27470-X [pii]
AID - 10.1111/j.1600-6143.2012.04060.x [doi]
PST - ppublish
SO  - Am J Transplant. 2012 Jun;12(6):1398-408. doi: 10.1111/j.1600-6143.2012.04060.x. 
      Epub 2012 Apr 14.