Background The expression of HLA-G during allogeneic recognition is associated with better graft acceptance. The inhibitory receptor ILT2 is expressed on activated T cells and serves to shut down T cell activation, culminating in T cell death or induction of anergy. One of the potential mechanisms in the immunosuppressive accomplishment of HLA-G-ILT2 interactions involves the expansion of myeloid-derived suppressor cells (MDSCs). The potential of MDSCs in transplantation has not yet been exploited. Methods (1) Detailed phenotypic characteristics, immunosuppressive potential of MDSCs expanded via inhibitory receptor ILT2 and its ligands, and allogeneic transplant-activated MDSCs were obtained in mice. (2) Oligo- and Real-time pathway-specific PCR Arrays were performed to characterize ILT2-specific MDSCs. (3) Skin allograft survival after adoptive transfer of MDSCs was studied. Results Engagement of ILT2 receptors, especially by HLA-G, expanded the population of MDSCs with enhanced suppressive activity. Adoptive transfer of MDSCs generated via ILT2 receptor and its ligands prolonged graft survival in recipients of allogeneic skin transplant. We have proposed pathways for enhancement of immunosuppressive activities and expansion of MDSCs via ILT2 and HLA-G. Conclusions Our results suggest that induction of MDSCs using ILT2 inhibitory receptor/HLA-G ligand may be an attractive strategy for preventing rejection of highly immunogenic organs/tissues in clinical transplantation.

We investigated the potency of exogenous bone marrow mesenchymal stem cells (MSCs) to engraft into irradiated intestine, as well as these cells' effects on radiation-induced enteric injury. MSCs from beta-Gal-transgenic mice were transplanted into C57BL/6J recipient mice that received abdominal irradiation (13 Gy). At different time points, recipient intestines were examined for the engraftment of donor-derived cells by immunofluorescence analysis. Additionally, the expression status of chemokines induced by radiation injury was analyzed in the irradiated intestine. Next, MSCs were transduced with an adenoviral vector encoding a certain chemokine receptor gene in order to promote the engraftment rate via chemotaxis. The intestinal permeability and histomorphological alterations were measured to evaluate the therapeutic effect of MSC transplantation. The results demonstrated that infused MSCs possessed the potency to engraft into irradiated enteric mucosa, but the engraftment rate was too low to produce a therapeutic effect. The expression of stromal cell-derived factor-1 (SDF-1) was up-regulated in irradiated intestine. MSCs genetically modified by CXCR4 (the receptor for SDF-1) engrafted into irradiated intestine at a significantly elevated level and ameliorated the intestinal permeability and histopathological damage.