10 Cotransplantation with HSC resulted in long-term survival in >60% islet allografts without requirement of immunosuppression, which was associated with enhanced CD8+ T-cell apoptosis, as well as a marked increase in Foxp3+ regulatory T (Treg) cells (increased from ∼10% in controls to ∼40% CD4+ cells). HSC eliminate antigen-specific activated CD8+ cells through the B7-H1 pathway; however, the mechanisms involved in Treg cells expansion remain unclear.11, 12 There is accumulating data suggesting that peripheral Treg cells are generated from naïve T cells by stimulation of particular subsets of antigen-presenting cells (APC) in lymph nodes (LN).13, 14 Even though HSC can modestly expand naturally existing Treg

cells in vitro,15 it is unlikely that HSC can directly induce large amounts of Treg cells in vivo because cotransplanted GFP-HSC do not show an ability to migrate to draining (d) LN (unpubl. data). We hypothesize that induction of Treg cells may be GDC-0941 molecular weight mediated by cells PLX4032 solubility dmso other than HSC. Myeloid-derived

suppressor cells (MDSC) were initially identified in cancer patients and contribute to cancer evasion from immune surveillance. They contain heterogeneous myeloid cell populations, but share some common characteristics: immature phenotype, inability to differentiate into mature myeloid cells, high expression of arginase 1, and a high potential to suppress immune response.16 In this study we provide both in vivo and selleck chemical in vitro evidence that HSC preferentially induce MDSC. These

effects are dependent on the interferon gamma (IFN-γ) signaling pathway in HSC and are mediated by soluble factor(s). APC, antigen-presenting cells; BM, bone marrow; CFSE, carboxyfluorescein diacetate succinimidyl ester; DC, dendritic cells; ELISA, enzyme-linked immunosorbent assay; Gr-1, granulocyte-differentiation antigen-1; H-MC, HSC-conditioned myeloid cells; hpf, high-power field; HSC, hepatic stellate cells; LN, lymph node; MLR, mixed leukocyte reaction; mAb, monoclonal antibody; MDSC, myeloid-derived suppressor cells; NPC, nonparenchymal cells; POD, postoperative day; qPCR, quantitative polymerase chain reaction; SMA, smooth muscle actin; Treg, T regulatory; WT, wildtype. Male C57BL/6J (B6, H2b), BALB/c (H2d), C3H (H2k), IFN-γR1−/−, granulocyte colony-stimulating factor (G-CSF)−/−, granulocyte-macrophage colony-stimulating factor (GM-CSF)−/−, and OT-I and OT-II TCR transgenic mice were purchased from Jackson Laboratory (Bar Harbor, ME). The mice with chicken oval albumin (OVA) specific expression on hepatocytes (OVA-HEP) were provided by Dr. Marion Peters (University of California, San Francisco, CA). B7-H1 knockout mice were provided by Dr. Lieping Chen (Johns Hopkins University Medical School, Baltimore, MD). All animals were maintained and used following National Institutes of Health (NIH) guidelines. (Please see Materials and Methods in Supporting Data for further details.