Preconditioning of NOD mice with anti-CD8 mAb and costimulatory blockade enhances chimerism and tolerance and prevents diabetes, while depletion of alpha beta-TCR+ and CD4+ cells negates the effect.

Bone marrow transplantation blocks diabetes pathogenesis and reverses autoimmunity in nonobese diabetic (NOD) mice. However, there is a greater barrier to engraftment in the context of autoimmunity. In the present study, we characterized which recipient cells influence engraftment in prediabetic NOD mice, with the goal to replace myelotoxic conditioning with antigen-specific deletion of reactive host cells.

Impact of bone marrow transplantation on type I diabetes.

Type I diabetes is a systemic autoimmune disease. Evidence is accumulating that autoimmune diseases such as type I diabetes are linked to the bone marrow hematopoietic stem cell (HSC) itself rather than its derivatives. HSC chimerism achieved through bone marrow transplantation (BMT) may affect type I diabetes in two ways: first, to induce tolerance to pancreas and islet cell transplants; and second, to reverse the autoimmune process prior to the development of terminal complications.

Alpha beta TCR+ T cells play a nonredundant role in the rejection of heart allografts in mice.

Background: Although the transplantation of solid organs and cellular grafts is a clinical routine, the morbidity and mortality associated with immunosuppression is significant. This could be avoided by the induction of donor-specific tolerance. To develop targeted antirejection strategies and regimens to induce donor-specific tolerance, cell populations in the recipient-mediating rejection of solid organ and cellular grafts must be defined.

Clinical applications of mixed chimerism.

Bone marrow transplantation (BMT) is currently a procedure that is associated with high morbidity and mortality. Thus, the clinical application of this technique is limited to the treatment of life-threatening hematopoietic malignancies. The morbidity and mortality of BMT is mainly related to graft-versus-host disease (GVHD), failure of engraftment, and toxicity related to fully myeloablative conditioning.

Effect of FLT3 ligand and granulocyte colony-stimulating factor on expansion and mobilization of facilitating cells and hematopoietic stem cells in mice: kinetics and repopulating potential.

We have previously identified a cellular population in murine bone marrow that facilitates engraftment of highly purified hematopoietic stem cells (HSC) across major histocompatibility complex (MHC) barriers without causing graft-versus-host disease. Here we investigated the effect of flt3 ligand (FL) and granulocyte colony-stimulating factor (G-CSF) on the mobilization of facilitating cells (FC) and HSC into peripheral blood (PB). Mice were injected with FL alone (day 1 to 10), G-CSF alone (day 4 to 10), or both in combination.