The free medial sural artery perforator flap transfer is appropriate for small- to medium-sized hand defect reconstruction. The donor site not only supplies a thin fasciocutaneous flap but also provides the option to harvest a segment of tendon or nerve graft through the same incision for composite tissue reconstruction in a single stage.
Aims/hypothesis A new differentiation pathway for CD4 − CD8 − (DN) T cells has recently been identified that exhibits the potent function of peripheral converted DN T cells in suppressing immune responses and provides the potential to treat autoimmune diseases. The aim of this study was to determine if the DN T cells converted from CD4 + T cells of NOD mice retain the antigen-specific regulatory capacity and prevent autoimmune diabetes in vivo. We also sought to determine if the combination of DN T cells with rapamycin promotes islet allograft survival in autoimmune diabetic NOD recipients. Methods NOD CD4 + T cells were converted to DN T cells in an in vitro mixed-lymphocyte reaction, with or without GAD65 peptide, as previously reported. The antigenspecific DN T cells were adoptively transferred to NOD/ SCID mice, new-onset diabetic NOD mice or isletallograft-recipient NOD mice as the part of cell-based therapy. The development of diabetes and allograft survival was assessed by monitoring blood glucose levels. Results NOD CD4 + T cells were converted in vitro to DN T cells at a rate of 50% and expressed unique cell features. The DN T cells from NOD donors blocked autoimmunity and prevented diabetes in NOD models, and these effects were even greater for GAD65-peptide-primed DN T cells. DN T cells acted in conjunction with rapamycin to suppress alloantigen-triggered T cell proliferation, promoted apoptosis and prolonged islet allograft survival in NOD recipients. Conclusions/interpretation Administration of the islet beta cell antigen-specific DN T cells can prevent the development of autoimmune diabetes and promote islet allograft survival in NOD mice.
This novel mouse model allows performing vascularized composite allotransplantation with very high success and survival rates. The advantages over conventional models are multifold. A high-flow common carotid artery keeps the anastomosis patent, and diastolic suction of the heart reduces the risk of venous stasis and thrombus formation. Less destruction because of the heterotopic positioning of the hindlimb graft further reduces the associated mortality and morbidity in this fragile model.
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