Ex Vivo–Expanded Human Regulatory T Cells Prevent the Rejection of Skin Allografts in a Humanized Mouse Model
- 27 December 2010
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Transplantation
- Vol. 90 (12), 1321-1327
- https://doi.org/10.1097/tp.0b013e3181ff8772
Abstract
Background. Composite tissue transplantation effectively reconstructs the most complex defects, but its use is limited because of harmful immunosuppression and the high susceptibility of skin to rejection. Development of tolerance is an ideal solution, and protocols using regulatory T cells (Tregs) to achieve this have been promising in experimental animal models. The aim of this study was to investigate the ability of human Tregs to regulate immune responses to a human skin allograft in vivo. Methods. We isolated and expanded naturally occurring CD127loCD25+CD4+ human Tregs from peripheral blood mononuclear cells (PBMCs) and examined their phenotype and suppressive activity in vitro. Using a clinically relevant chimeric humanized mouse system, we transplanted mice with human skin grafts followed by allogeneic populations of PBMCs with or without Tregs derived from the same PBMC donor. Results. Ex vivo–expanded Tregs maintain the appropriate Treg markers and retain suppressive activity against allostimulated and polyclonally stimulated autologous PBMCs in vitro. Mice receiving allogeneic PBMCs alone consistently reject human skin grafts, whereas those also receiving Tregs display stable long-term human skin transplant survival along with a reduction in the CD8+ human cellular graft infiltrate. Conclusions. We show for the first time the unique ability of human Tregs to prevent the rejection of a skin allograft in vivo, highlighting the therapeutic potential of these cells clinically.Keywords
This publication has 28 references indexed in Scilit:
- Hand transplantation in the United States: Experience with 3 patientsSurgery, 2008
- Science of Composite Tissue AllotransplantationTransplantation, 2008
- The International Registry on Hand and Composite Tissue TransplantationTransplantation, 2008
- Interferon-γ Conditioning Ex Vivo Generates CD25+CD62L+Foxp3+ Regulatory T Cells That Prevent Allograft Rejection: Potential Avenues for Cellular TherapyTransplantation, 2008
- Location and Time-Dependent Control of Rejection by Regulatory T Cells Culminates in a Failure to Generate Memory T CellsThe Journal of Immunology, 2008
- CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cellsThe Journal of Experimental Medicine, 2006
- Combined Treatment with CD40 Costimulation Blockade, T-Cell Depletion, Low-Dose Irradiation, and Donor Bone Marrow Transfusion in Limb Allograft SurvivalAnnals of Plastic Surgery, 2005
- CD25+CD4+ regulatory T cells generated by exposure to a model protein antigen prevent allograft rejection: antigen-specific reactivation in vivo is critical for bystander regulationBlood, 2005
- Only the CD62L+ subpopulation of CD4+CD25+ regulatory T cells protects from lethal acute GVHDBlood, 2005
- Rejection of the Component Tissues of Limb Allografts in Rats Immunosuppressed with FK-506 and CyclosporinePlastic and Reconstructive Surgery, 1996