PMID- 17932417
OWN - NLM
STAT- MEDLINE
DCOM- 20080325
LR  - 20220419
IS  - 1549-4918 (Electronic)
IS  - 1066-5099 (Linking)
VI  - 26
IP  - 1
DP  - 2008 Jan
TI  - Human leukocyte antigen-G5 secretion by human mesenchymal stem cells is required 
      to suppress T lymphocyte and natural killer function and to induce 
      CD4+CD25highFOXP3+ regulatory T cells.
PG  - 212-22
AB  - Adult bone marrow-derived mesenchymal stem cells (MSCs) are multipotent cells 
      that are the subject of intense investigation in regenerative medicine. In 
      addition, MSCs possess immunomodulatory properties with therapeutic potential to 
      prevent graft-versus-host disease (GvHD) in allogeneic hematopoietic cell 
      transplantation. Indeed, MSCs can inhibit natural killer (NK) function, modulate 
      dendritic cell maturation, and suppress allogeneic T-cell response. Here, we 
      report that the nonclassic human leukocyte antigen (HLA) class I molecule HLA-G 
      is responsible for the immunomodulatory properties of MSCs. Our data show that 
      MSCs secrete the soluble isoform HLA-G5 and that such secretion is 
      interleukin-10-dependent. Moreover, cell contact between MSCs and allostimulated 
      T cells is required to obtain a full HLA-G5 secretion and, as consequence, a full 
      immunomodulation from MSCs. Blocking experiments using neutralizing anti-HLA-G 
      antibody demonstrate that HLA-G5 contributes first to the suppression of 
      allogeneic T-cell proliferation and then to the expansion of 
      CD4(+)CD25(high)FOXP3(+) regulatory T cells. Furthermore, we demonstrate that in 
      addition to their action on the adaptive immune system, MSCs, through HLA-G5, 
      affect innate immunity by inhibiting both NK cell-mediated cytolysis and 
      interferon-gamma secretion. Our results provide evidence that HLA-G5 secreted by 
      MSCs is critical to the suppressive functions of MSCs and should contribute to 
      improving clinical therapeutic trials that use MSCs to prevent GvHD.
FAU - Selmani, Zohair
AU  - Selmani Z
AD  - Institut National de la Sante et de la Recherche Medicale U645, IFR 133, 
      Universite de Franche-Comte, Etablissement Francais du Sang 
      Bourgogne-Franche-Comte, Besancon, France.
FAU - Naji, Abderrahim
AU  - Naji A
FAU - Zidi, Ines
AU  - Zidi I
FAU - Favier, Benoit
AU  - Favier B
FAU - Gaiffe, Emilie
AU  - Gaiffe E
FAU - Obert, Laurent
AU  - Obert L
FAU - Borg, Christophe
AU  - Borg C
FAU - Saas, Philippe
AU  - Saas P
FAU - Tiberghien, Pierre
AU  - Tiberghien P
FAU - Rouas-Freiss, Nathalie
AU  - Rouas-Freiss N
FAU - Carosella, Edgardo D
AU  - Carosella ED
FAU - Deschaseaux, Frederic
AU  - Deschaseaux F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071011
PL  - England
TA  - Stem Cells
JT  - Stem cells (Dayton, Ohio)
JID - 9304532
RN  - 0 (CD4 Antigens)
RN  - 0 (FOXP3 protein, human)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (HLA Antigens)
RN  - 0 (HLA-G Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Interleukin-2 Receptor alpha Subunit)
RN  - 130068-27-8 (Interleukin-10)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Adult Stem Cells/cytology/immunology/metabolism
MH  - Blotting, Western
MH  - Bone Marrow Cells/cytology/immunology/metabolism
MH  - CD4 Antigens/metabolism
MH  - Cell Communication
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Flow Cytometry
MH  - Forkhead Transcription Factors/metabolism
MH  - HLA Antigens/*metabolism
MH  - HLA-G Antigens
MH  - Histocompatibility Antigens Class I/*metabolism
MH  - Humans
MH  - Interferon-gamma
MH  - Interleukin-10
MH  - Interleukin-2 Receptor alpha Subunit/metabolism
MH  - Killer Cells, Natural/immunology/*metabolism
MH  - Lymphocyte Culture Test, Mixed
MH  - Mesenchymal Stem Cells/cytology/immunology/*metabolism
MH  - Microscopy, Confocal
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - T-Lymphocyte Subsets/immunology/*metabolism
MH  - T-Lymphocytes, Cytotoxic/immunology/*metabolism
MH  - T-Lymphocytes, Regulatory/immunology/*metabolism
EDAT- 2007/10/13 09:00
MHDA- 2008/03/26 09:00
CRDT- 2007/10/13 09:00
PHST- 2007/10/13 09:00 [pubmed]
PHST- 2008/03/26 09:00 [medline]
PHST- 2007/10/13 09:00 [entrez]
AID - 2007-0554 [pii]
AID - 10.1634/stemcells.2007-0554 [doi]
PST - ppublish
SO  - Stem Cells. 2008 Jan;26(1):212-22. doi: 10.1634/stemcells.2007-0554. Epub 2007 
      Oct 11.