A potential possible therapy, Myoblast Transfer Therapy (MTT), for the lethal childhood myopathy Duchenne Muscular Dystrophy (DMD), is the transplantation of myogenic cells (myoblasts) into the diseased skeletal muscle in order to replace the missing gene product, dystrophin. To date, experimental studies in animal models and clinical trials of this therapy in patients have shown little or no s...

Mesenchymal stem cells (MSCs) are multipotent progenitor cells that have emerged as a promising tool for clinical application. Further clinical interest has been raised by the observation that MSCs are immunoprivileged and, more important, display immunosuppressive capacities. These properties may be of therapeutic value in allogeneic transplantation to prevent graft rejection and to prevent an...

Mice bearing disseminated syngeneic FBL-3 leukemia were treated with cyclophosphamide plus long term-cultured T cells immune to FBL-3. The cultured T cells for therapy had been induced to grow in vitro for 62 d by intermittent stimulation with irradiated FBL-3. At the time of therapy, such antigen-driven long term-cultured T cells were greatly expanded in number, proliferated in vitro in respon...

The intrathymic transfer of semiallogeneic CD4/CD8 double-negative (DN) thymocyte stem cells into irradiated host mice resulted in a transient state of chimerism in adoptive host thymus, spleen, and lymph nodes. Host-derived T cells, isolated from the thymus and periphery of the chimeric mice, were found to be specifically nonresponsive to the MHC antigens of the semiallogeneic DN donor in cyto...

Alterations in inhibitory receptor expression on NK cells have been detected in mixed allogeneic chimeras and in mosaic MHC class I-expressing transgenic mice. However, it is not known whether or not NK cells are tolerant to host and donor Ags in mixed chimeras. In vitro studies have shown a lack of mutual tolerance of separated donor and host NK cells obtained from mixed chimeras. Using BALB/c...

Bone marrow transplantation from diabetes-resistant strains with complete replacement of the recipient immune system by the allogeneic donor has led to tolerance to donor islets and cure of diabetes in a mouse model of type 1 diabetes. However, the ability to tolerize host T-cells of diabetic NOD mice is unknown. We demonstrate that nonmyeloablative conditioning achieves mixed hematopoietic chi...

Dendritic cells (DCs) are the most potent antigen presenting cells. DCs play a pivotal role in determining the character and magnitude of immune responses to tumors. Host and donor hematopoietic-derived DCs play a critical role in the development of graft-versus-host disease (GVHD) following allogeneic hematopoietic cell transplantation. GVHD is tightly linked with the graft-versus-tumor (GVT) ...

Allogeneic bone marrow transplantation is a curative treatment for leukemia and lymphoma, but graft-vs-host disease (GVHD) remains a major complication. Using a GVHD protective nonmyeloablative conditioning regimen of total lymphoid irradiation and antithymocyte serum (TLI/ATS) in mice that has been recently adapted to clinical studies, we show that regulatory host NKT cells prevent the expansi...