Frontiers in Immunology (Nov 2015)

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

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

DOI
https://doi.org/10.3389/fimmu.2015.00596
Journal volume & issue
Vol. 6

Abstract

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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.

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