No abstract

Using rapid prototyping technology, three-dimensional (3D) structures composed of hepatocytes and gelatin hydrogel have been formed. This technique employs a highly accurate 3D micropositioning system with a pressure-controlled syringe to deposit cell/biomaterial structures with a lateral resolution of 10 microm. The pressure-activated micro-syringe is equipped with a fine-bore exit needle for which a wide variety of 3D patterns with different arrays of channels (through-holes) were created. More than 30 layers of a hepatocyte/gelatin mixture were laminated into a high spacial structure using this method. The laminated hepatocytes remained viable and performed biological functions in the construct for more than 2 months. The rapid prototyping technology offers potential for eventual high-throughout production of artificial human tissues or organs.

Key Points Low doses of adoptively transferred donor CD4+ iNKT cells protect from GVHD while preserving graft-versus-tumor effects. Donor CD4+ iNKT cells inhibit proliferation of alloreactive T cells and promote robust expansion of donor Tregs.

Key Points TNF-α produced during aGVHD is a strong and selective activator of CD4+CD25+FoxP3+ Tregs. In vitro TNF-α priming enhances CD4+CD25+FoxP3+ Treg proliferation and their ability to protect from GVHD.

Foxp3+ regulatory T cells (Treg cells) modulate the immune system and maintain self-tolerance, but whether they affect haematopoiesis or haematopoietic stem cell (HSC)-mediated reconstitution after transplantation is unclear. Here we show that B-cell lymphopoiesis is impaired in Treg-depleted mice, yet this reduced B-cell lymphopoiesis is rescued by adoptive transfer of affected HSCs or bone marrow cells into Treg-competent recipients. B-cell reconstitution is abrogated in both syngeneic and allogeneic transplantation using Treg-depleted mice as recipients. Treg cells can control physiological IL-7 production that is indispensable for normal B-cell lymphopoiesis and is mainly sustained by a subpopulation of ICAM1+ perivascular stromal cells. Our study demonstrates that Treg cells are important for B-cell differentiation from HSCs by maintaining immunological homoeostasis in the bone marrow microenvironment, both in physiological conditions and after bone marrow transplantation.