HLA-G level on monocytoid dendritic cells correlates with regulatory T-cell Foxp3 expression in liver transplant tolerance.
HLA-G level on monocytoid dendritic cells correlates with regulatory T-cell Foxp3 expression in liver transplant tolerance.
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DOI：
10.1097/tp.0b013e31821414c9
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发表时间：
2011-05-27
期刊：
影响因子：
6.2
通讯作者：
Thomson AW
中科院分区：
文献类型：
--
作者：
Castellaneta A;Mazariegos GV;Nayyar N;Zeevi A;Thomson AW
Human leukocyte antigen (HLA)-G is a non-classical HLA class I molecule expressed as membrane-bound and soluble isoforms. Interaction of HLA-G with its receptor, immunoglobulin (Ig)-like transcript (ILT) 4 on dendritic cells (DC) down-regulates their T cell stimulatory ability. We examined expression of HLA-G, ILT4, other immune regulatory molecules (inducible costimulator ligand and glucocorticoid-induced tumor necrosis factor-related receptor ligand), and the activation marker CMRF44 on circulating monocytoid (m) and plasmacytoid (p)DC by monoclonal antibody staining and flow cytometry. Three groups of stable liver transplant recipients,-operationally tolerant (TOL), prospective immunosuppressive drug weaning (PW) and maintenance immunosuppression (MI) were studied, together with healthy controls (HC). Serum HLA-G levels were measured by enzyme-linked immunosorbent assay. In TOL patients, mDC but not pDC expressed higher HLA-G than in MI patients or HC. In TOL patients, the incidence of CD4+CD25hiCD127− 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 >100ng/ml was highest in the TOL group, although statistical significance was not achieved. 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.
