title: Alloreactive Regulatory T Cells Allow the Generation of Mixed Chimerism and Transplant Tolerance.
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.
authors.affiliation: Departmento de Biología, Facultad de Ciencias, Universidad de Chile , Santiago , Chile ; Departamento de Tecnología Médica, Facultad de Medicina, Universidad de Chile , Santiago , Chile.
authors.forename: Paulina
authors.initials: P
authors.lastname: Ruiz
authors.affiliation: Departmento de Biología, Facultad de Ciencias, Universidad de Chile , Santiago , Chile.
authors.forename: Paula
authors.initials: P
authors.lastname: Maldonado
authors.affiliation: Departmento de Biología, Facultad de Ciencias, Universidad de Chile , Santiago , Chile.
authors.forename: Yessia
authors.initials: Y
authors.lastname: Hidalgo
authors.affiliation: Departmento de Biología, Facultad de Ciencias, Universidad de Chile , Santiago , Chile.
authors.forename: Daniela
authors.initials: D
authors.lastname: Sauma
authors.affiliation: Departmento de Biología, Facultad de Ciencias, Universidad de Chile , Santiago , Chile ; Fundación Ciencia y Vida , Santiago , Chile ; Facultad de Ciencias Biológicas, Universidad Andres Bello , Santiago , Chile.
authors.forename: Mario
authors.initials: M
authors.lastname: Rosemblatt
authors.affiliation: Departmento de Biología, Facultad de Ciencias, Universidad de Chile , Santiago , Chile.
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Bono
keywords: alloreactive regulatory T cells; mixed chimerism; non-myeloablative conditioning; organ transplantation; transplant tolerance