Ruiz Paulina, Maldonado Paula, Hidalgo Yessia, Sauma Daniela, Rosemblatt Mario, Bono Maria Rosa
Departmento de Biología, Facultad de Ciencias, Universidad de Chile , Santiago , Chile ; Departamento de Tecnología Médica, Facultad de Medicina, Universidad de Chile , Santiago , Chile.
Departmento de Biología, Facultad de Ciencias, Universidad de Chile , Santiago , Chile.
Front Immunol. 2015 Nov 23;6:596. doi: 10.3389/fimmu.2015.00596. eCollection 2015.
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.
诱导供体特异性移植耐受是现代免疫学的主要目标之一。在移植受者中建立混合嵌合状态已被证明是诱导长期同种异体移植耐受的合适策略；然而，目前的实验性受者预处理方案有许多副作用，并且在未来治疗中不可行。为了改进当前的混合嵌合诱导方案，我们开发了一种非清髓性骨髓移植（NM-BMT）方案，该方案使用视黄酸（RA）诱导的同种异体抗原特异性调节性T细胞、临床可用的免疫抑制药物和较低剂量的辐射。我们证明，除了NM-BMT方案外，RA诱导的同种异体抗原特异性调节性T细胞可产生稳定的混合嵌合状态，并诱导小鼠对同种异体二次皮肤移植产生耐受。因此，通过使用供体特异性调节性T细胞而非非特异性免疫抑制来建立混合嵌合状态在器官移植中可能具有潜在用途。
