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

Paulina Ruiz, Paula Maldonado, Yessia Hidalgo, Daniela Sauma, Mario Rosemblatt, Maria Rosa Bono

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

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 (NM-BMT) protocol using retinoic acid (RA)-induced alloantigen-specific Tregs, clinically available immunosuppressive drugs, and lower doses of irradiation. We demonstrate that RA-induced alloantigen-specific Tregs in addition to a NM-BMT protocol generates stable mixed chimerism and induces 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.

Original languageEnglish
Article number596
JournalFrontiers in Immunology
Volume6
Issue numberNOV
DOIs
Publication statusPublished - 2015

Keywords

  • Alloreactive regulatory T cells
  • Mixed chimerism
  • Non-myeloablative conditioning
  • Organ transplantation
  • Transplant tolerance

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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