PMID- 23810844
OWN - NLM
STAT- MEDLINE
DCOM- 20140317
LR  - 20230708
IS  - 1523-6536 (Electronic)
IS  - 1083-8791 (Linking)
VI  - 19
IP  - 9
DP  - 2013 Sep
TI  - Enrichment of IL-12-producing plasmacytoid dendritic cells in donor bone marrow 
      grafts enhances graft-versus-leukemia activity in allogeneic hematopoietic stem 
      cell transplantation.
PG  - 1331-9
LID - S1083-8791(13)00287-5 [pii]
LID - 10.1016/j.bbmt.2013.06.016 [doi]
AB  - A critical question in the field of allogeneic hematopoietic stem cell 
      transplantation (HSCT) is how to enhance graft-versus-leukemia (GVL) activity 
      while limiting graft-versus-host-disease (GVHD). We have previously reported that 
      donor bone marrow (BM) precursors of plasmacytoid dendritic cells (pre-pDCs) can 
      polarize donor T cells toward Th1 immunity and augment the GVL activity of donor 
      T cells while attenuating their GVHD activity in a murine model of allogeneic 
      HSCT. Clinical data on the role of donor pre-pDCs and conventional DCs (cDCs) on 
      transplantation outcomes has been conflicting. To test the effect of increasing 
      the proportion of pre-pDCs versus cDCs in a BM graft, we enriched CD11b(-) pDCs 
      by selectively depleting the CD11b(+) myeloid DC (mDC) population from BM using 
      FACS sorting in a murine model of allogeneic BM transplantation. Donor T cell 
      expansion and GVL activity were greater in mice that received BM depleted of mDCs 
      compared with mice that received undepleted BM. GVHD was not increased by 
      depleting mDCs. To examine the mechanism through which mDC depletion enhances the 
      GVL activity of donor T cells, we used BM and pDCs from IL-12p40KO mice, and 
      found that the increased GVL activity of mDC-depleted BM was IL-12-dependent. 
      This study indicates that a clinically translatable strategy of engineering the 
      DC content of grafts can improve clinical outcomes in allogeneic HSCT through the 
      regulation of donor T cell activation and GVL activity.
CI  - Copyright (c) 2013 American Society for Blood and Marrow Transplantation. Published 
      by Elsevier Inc. All rights reserved.
FAU - Darlak, Katarzyna A
AU  - Darlak KA
AD  - Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory 
      University, Atlanta, Georgia, USA.
FAU - Wang, Ying
AU  - Wang Y
FAU - Li, Jian-Ming
AU  - Li JM
FAU - Harris, Wayne A C
AU  - Harris WA
FAU - Owens, Lauren M
AU  - Owens LM
FAU - Waller, Edmund K
AU  - Waller EK
LA  - eng
GR  - R01 CA074364/CA/NCI NIH HHS/United States
GR  - R01 CA188523/CA/NCI NIH HHS/United States
GR  - R56 AI145231/AI/NIAID NIH HHS/United States
PT  - Journal Article
DEP - 20130627
PL  - United States
TA  - Biol Blood Marrow Transplant
JT  - Biology of blood and marrow transplantation : journal of the American Society for 
      Blood and Marrow Transplantation
JID - 9600628
RN  - 187348-17-0 (Interleukin-12)
SB  - IM
MH  - Animals
MH  - Bone Marrow Transplantation/*methods
MH  - Cell Proliferation
MH  - Dendritic Cells/immunology/*transplantation
MH  - Graft vs Host Disease/immunology
MH  - Graft vs Leukemia Effect/immunology
MH  - Hematopoietic Stem Cell Transplantation/*methods
MH  - Interleukin-12/biosynthesis/*immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - T-Lymphocytes/immunology/transplantation
MH  - Transplantation, Homologous
OTO - NOTNLM
OT  - Dendritic cell T cell
OT  - Graft-versus-leukemia
OT  - IL-12
EDAT- 2013/07/03 06:00
MHDA- 2014/03/19 06:00
CRDT- 2013/07/02 06:00
PHST- 2012/10/31 00:00 [received]
PHST- 2013/06/18 00:00 [accepted]
PHST- 2013/07/02 06:00 [entrez]
PHST- 2013/07/03 06:00 [pubmed]
PHST- 2014/03/19 06:00 [medline]
AID - S1083-8791(13)00287-5 [pii]
AID - 10.1016/j.bbmt.2013.06.016 [doi]
PST - ppublish
SO  - Biol Blood Marrow Transplant. 2013 Sep;19(9):1331-9. doi: 
      10.1016/j.bbmt.2013.06.016. Epub 2013 Jun 27.