PMID- 21423069
OWN - NLM
STAT- MEDLINE
DCOM- 20110630
LR  - 20211020
IS  - 1534-6080 (Electronic)
IS  - 0041-1337 (Print)
IS  - 0041-1337 (Linking)
VI  - 91
IP  - 10
DP  - 2011 May 27
TI  - HLA-G level on monocytoid dendritic cells correlates with regulatory T-cell Foxp3 
      expression in liver transplant tolerance.
PG  - 1132-40
LID - 10.1097/TP.0b013e31821414c9 [doi]
AB  - BACKGROUND: Human leukocyte antigen (HLA)-G is a nonclassical HLA class I 
      molecule expressed as membrane-bound and soluble isoforms. Interaction of HLA-G 
      with its receptor, immunoglobulin-like transcript 4 on dendritic cells (DCs) 
      down-regulates their T-cell stimulatory ability. METHODS: We examined expression 
      of HLA-G, immunoglobulin-like transcript 4, other immune regulatory molecules 
      (inducible costimulator ligand and glucocorticoid-induced tumor necrosis 
      factor-related receptor ligand), and the activation marker CMRF44 on circulating 
      monocytoid dendritic cell (mDC) and plasmacytoid dendritic cell by monoclonal 
      antibody staining and flow cytometry. Three groups of stable liver transplant 
      recipients: operationally tolerant (TOL), prospective immunosuppressive drug 
      weaning, and maintenance immunosuppression (MI) were studied, together with 
      healthy controls (HC). Serum HLA-G levels were measured by enzyme-linked 
      immunosorbent assay. RESULTS: In TOL patients, monocytoid dendritic cell (mDC) 
      but not plasmacytoid dendritic cell expressed higher HLA-G than in MI patients or 
      HC. In TOL patients, the incidence of CD4(+)CD25(hi)CD127(-) regulatory T cells 
      (Treg) and the intensity of Treg forkhead box p3 (Foxp3) expression were 
      significantly higher than in the MI group. HLA-G expression on circulating mDC 
      correlated significantly with that of Foxp3 in the TOL group. There was no 
      correlation between immunosuppressive drug (tacrolimus) dose or trough level and 
      HLA-G expression or Treg frequency or Foxp3 expression. The incidence of patients 
      with circulating HLA-G levels more than 100 ng/mL was highest in the TOL group, 
      although statistical significance was not achieved. CONCLUSIONS: Higher HLA-G 
      expression on circulating mDC in TOL recipients compared with MI or HC, suggests 
      a possible role of HLA-G in immune regulation possibly mediated by enhanced host 
      Treg Foxp3 expression.
FAU - Castellaneta, Antonino
AU  - Castellaneta A
AD  - Department of Surgery, Thomas E. Starzl Transplantation Institute, University of 
      Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
FAU - Mazariegos, George V
AU  - Mazariegos GV
FAU - Nayyar, Navdeep
AU  - Nayyar N
FAU - Zeevi, Adriana
AU  - Zeevi A
FAU - Thomson, Angus W
AU  - Thomson AW
LA  - eng
GR  - UL1 RR024153/RR/NCRR NIH HHS/United States
GR  - P01 AI081678/AI/NIAID NIH HHS/United States
GR  - P01 AI081678-02/AI/NIAID NIH HHS/United States
GR  - P01 AI081678-01/AI/NIAID NIH HHS/United States
GR  - UL1 TR000005/TR/NCATS NIH HHS/United States
GR  - P01 AI81678/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (Antigens, CD)
RN  - 0 (Biomarkers)
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 (ICOSLG protein, human)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Inducible T-Cell Co-Stimulator Ligand)
RN  - 0 (LILRB2 protein, human)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (TNFSF18 protein, human)
RN  - 0 (Tumor Necrosis Factors)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Antigens, CD/blood
MH  - Biomarkers/blood
MH  - Child
MH  - Dendritic Cells/drug effects/*immunology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Flow Cytometry
MH  - Forkhead Transcription Factors/*blood
MH  - HLA Antigens/*blood
MH  - HLA-G Antigens
MH  - Histocompatibility Antigens Class I/*blood
MH  - Humans
MH  - Immunosuppressive Agents/administration & dosage
MH  - Inducible T-Cell Co-Stimulator Ligand
MH  - Liver Transplantation/*immunology
MH  - Male
MH  - Membrane Glycoproteins/blood
MH  - Middle Aged
MH  - Pennsylvania
MH  - Receptors, Immunologic/blood
MH  - T-Lymphocytes, Regulatory/drug effects/*immunology
MH  - *Transplantation Tolerance
MH  - Tumor Necrosis Factors/blood
MH  - Young Adult
PMC - PMC3087844
MID - NIHMS278598
COIS- Conflict of interest disclosure The authors of this manuscript declare no 
      conflicts of interest.
EDAT- 2011/03/23 06:00
MHDA- 2011/07/01 06:00
PMCR- 2012/05/27
CRDT- 2011/03/23 06:00
PHST- 2011/03/23 06:00 [entrez]
PHST- 2011/03/23 06:00 [pubmed]
PHST- 2011/07/01 06:00 [medline]
PHST- 2012/05/27 00:00 [pmc-release]
AID - 10.1097/TP.0b013e31821414c9 [doi]
PST - ppublish
SO  - Transplantation. 2011 May 27;91(10):1132-40. doi: 10.1097/TP.0b013e31821414c9.