PMID- 23582182
OWN - NLM
STAT- MEDLINE
DCOM- 20150514
LR  - 20220409
IS  - 1555-3892 (Electronic)
IS  - 0963-6897 (Linking)
VI  - 23
IP  - 9
DP  - 2014
TI  - Adult human hepatocytes promote CD4(+) T-cell hyporesponsiveness via 
      interleukin-10-producing allogeneic dendritic cells.
PG  - 1127-42
LID - 10.3727/096368913X666421 [doi]
AB  - The success of liver cell therapy remains closely dependent on how well the 
      infused cells can be accepted after transplantation and is directly related to 
      their degree of immunogenicity. In this study, we investigated the in vitro 
      immunogenic properties of isolated human hepatocytes (hHeps) and adult-derived 
      human liver progenitor cells (ADHLPCs), an alternative cell candidate for liver 
      cell transplantation (LCT). The constitutive expression of immune markers was 
      first analyzed on these liver-derived cells by flow cytometry. Human 
      liver-derived cells were then cocultured with allogeneic human adult peripheral 
      blood mononuclear cells (PBMCs), and the resulting activation and proliferation 
      of PBMCs was evaluated, as well as the cytokine levels in the coculture 
      supernatant. The effect of liver-derived cells on monocyte-derived dendritic cell 
      (MoDC) properties was further analyzed in a secondary coculture with naive CD4(+) 
      T-cells. We report that hHeps and ADHLPCs expressed human leukocyte antigen (HLA) 
      class I and Fas but did not express HLA-DR, Fas ligand, and costimulatory 
      molecules. hHeps and ADHLPCs did not induce T-cell activation or proliferation. 
      Moreover, hHeps induced a cell contact-dependent production of interleukin 
      (IL)-10 that was not observed with ADHLPCs. The IL-10 was produced by a myeloid 
      DC subset characterized by an incomplete mature state. Furthermore, hHep-primed 
      MoDCs induced an antigen-independent hyporesponsiveness of naive CD4(+) T 
      lymphocytes that was partially reversed by blocking IL-10, whereas nonprimed 
      MoDCs (i.e., those cultured alone) did not. hHeps and ADHLPCs present a low 
      immunogenic phenotype in vitro. Allogeneic hHeps, but not ADHLPCs, promote a cell 
      contact-dependent production of IL-10 by myeloid DCs, which induces naive CD4(+) 
      T-cells antigen-independent hyporesponsiveness.
FAU - Sana, Gwenaelle
AU  - Sana G
AD  - Universite Catholique de Louvain and Cliniques Universitaires Saint-Luc, 
      Laboratory of Pediatric Hepatology and Cell Therapy, Brussels, Belgium.
FAU - Lombard, Catherine
AU  - Lombard C
FAU - Vosters, Olivier
AU  - Vosters O
FAU - Jazouli, Nawal
AU  - Jazouli N
FAU - Andre, Floriane
AU  - Andre F
FAU - Stephenne, Xavier
AU  - Stephenne X
FAU - Smets, Francoise
AU  - Smets F
FAU - Najimi, Mustapha
AU  - Najimi M
FAU - Sokal, Etienne M
AU  - Sokal EM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Transplant
JT  - Cell transplantation
JID - 9208854
RN  - 0 (Cytokines)
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - CD4-Positive T-Lymphocytes/cytology/*immunology
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - Child
MH  - Coculture Techniques
MH  - Cytokines/metabolism
MH  - Dendritic Cells/*cytology/metabolism
MH  - Female
MH  - Hepatocytes/*cytology
MH  - Humans
MH  - Infant
MH  - Interleukin-10/*metabolism
MH  - Leukocytes, Mononuclear/cytology
MH  - Liver/cytology/metabolism
MH  - Lymphocyte Activation
MH  - Male
MH  - Middle Aged
MH  - Monocytes/cytology
MH  - Stem Cells/cytology
MH  - Transplantation, Homologous
EDAT- 2013/04/16 06:00
MHDA- 2015/05/15 06:00
CRDT- 2013/04/16 06:00
PHST- 2013/04/16 06:00 [entrez]
PHST- 2013/04/16 06:00 [pubmed]
PHST- 2015/05/15 06:00 [medline]
AID - content-cog_09636897_ct0617sana [pii]
AID - 10.3727/096368913X666421 [doi]
PST - ppublish
SO  - Cell Transplant. 2014;23(9):1127-42. doi: 10.3727/096368913X666421.