PMID- 19150657
OWN - NLM
STAT- MEDLINE
DCOM- 20090817
LR  - 20090504
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 9
IP  - 6
DP  - 2009 Jun
TI  - Induction of tolerance in organ recipients by hematopoietic stem cell 
      transplantation.
PG  - 694-700
LID - 10.1016/j.intimp.2008.12.009 [doi]
AB  - The use of hematopoietic stem cell transplantation (HSCT) for the establishment 
      of mixed chimerism represents a viable and attractive approach for generating 
      tolerance in transplantation biology, as it generally leads to durable immune 
      tolerance, enabling the subsequent engraftment of organ transplants without the 
      need for a deleterious continuous immunosuppressive therapy. However, in order to 
      apply HSCT to patients in a manner that enables long term survival, 
      transplant-related mortality must be minimized by eliminating the risk for 
      graft-versus-host-disease (GVHD) and by reducing the toxicity of the conditioning 
      protocol. T-cell depleted bone marrow transplants (TDBMT) have been shown to 
      adequately eliminate GVHD. However, even in leukemia patients undergoing 
      supralethal conditioning, mismatched TDBMT are vigorously rejected. This barrier 
      can be overcome through the modulatory activity of CD34 cells, which are endowed 
      with veto activity, by the use of megadose stem cell transplants. In mice, 
      megadoses of Sca+lin-hematopoietic stem cells can induce mixed chimerism 
      following sub-lethal conditioning. Nevertheless, the number of human CD34 cells 
      that can be harvested is not likely to be sufficient to overcome rejection under 
      reduced intensity conditioning (RIC), which might be acceptable in recipients of 
      organ transplantation. To address this challenge, we investigated a novel source 
      of veto cells, namely anti 3rd-party cytotoxic T cells (CTLs) which are depleted 
      of GVH reactivity, combined with megadoses of purified stem cells and a RIC 
      protocol. This approach might provide a safer modality for the induction of 
      durable chimerism.
FAU - Ophir, Eran
AU  - Ophir E
AD  - Weizmann Institute of Science, Department of Immunology, Rehovot 76100, Israel.
FAU - Reisner, Yair
AU  - Reisner Y
LA  - eng
GR  - 5 U19 CA100265-03/CA/NCI NIH HHS/United States
GR  - 5P01 CA049639/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090116
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
SB  - IM
MH  - Animals
MH  - Graft vs Host Disease/*immunology/prevention & control
MH  - *Hematopoietic Stem Cell Transplantation
MH  - Hematopoietic Stem Cells/*immunology
MH  - Humans
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - T-Lymphocytes, Cytotoxic/immunology
MH  - Transplantation Conditioning/*methods
MH  - *Transplantation Tolerance
EDAT- 2009/01/20 09:00
MHDA- 2009/08/18 09:00
CRDT- 2009/01/20 09:00
PHST- 2008/11/11 00:00 [received]
PHST- 2008/11/19 00:00 [revised]
PHST- 2008/12/10 00:00 [accepted]
PHST- 2009/01/20 09:00 [entrez]
PHST- 2009/01/20 09:00 [pubmed]
PHST- 2009/08/18 09:00 [medline]
AID - S1567-5769(08)00380-9 [pii]
AID - 10.1016/j.intimp.2008.12.009 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2009 Jun;9(6):694-700. doi: 10.1016/j.intimp.2008.12.009. 
      Epub 2009 Jan 16.