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Alloreactive regulatory T cells allow the generation of mixed chimerism and transplant tolerance

By Paulina eRuiz, Paulina eRuiz, Paula eMaldonado, Yessia eHidalgo, Daniela eSauma, Mario eRosemblatt, Mario eRosemblatt, Mario eRosemblatt and Maria Rosa eBono

Abstract

The induction of donor-specific transplant tolerance is one of the main goals of modern immunology. Establishment of a mixed chimerism state in the transplant recipient has proven to be a suitable strategy for the induction of long-term allograft tolerance; however, current experimental recipient preconditioning protocols have many side effects, and are not feasible for use in future therapies. In order to improve the current mixed chimerism induction protocols, we developed a non-myeloablative bone-marrow transplant protocol using retinoic acid induced alloantigen-specific Tregs, clinically available immunosuppressive drugs and lower doses of irradiation. We demonstrate that retinoic acid induced alloantigen-specific Tregs in addition to a non-myeloablative bone-marrow transplant protocol generates stable mixed chimerism and induce tolerance to allogeneic secondary skin allografts in mice. Therefore, the establishment of mixed chimerism through the use of donor-specific Tregs rather than non-specific immunosuppression could have a potential use in organ transplantation

Topics: Organ Transplantation, transplant tolerance, mixed chimerism, Non-myeloablative conditioning, Alloreactive regulatory T cells, Immunologic diseases. Allergy, RC581-607
Publisher: Frontiers Media S.A.
Year: 2015
DOI identifier: 10.3389/fimmu.2015.00596
OAI identifier: oai:doaj.org/article:4023d2c7dff64a4093597addd3f56f5e
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