Domen Jos, Li Yongwu, Sun Lei, Simpson Pippa, Gandy Kimberly
Section of Cardiac Surgery, Children's Mercy Hospital and Clinics, Kansas City MO64108, United States; Department of Pediatrics, University of Missouri Kansas City, Kansas City, MO, United States.
Section of Cardiac Surgery, Children's Mercy Hospital and Clinics, Kansas City MO64108, United States.
Transpl Immunol. 2014 Aug;31(2):112-8. doi: 10.1016/j.trim.2014.04.001. Epub 2014 Apr 30.
Donor specific hematopoietic cell transplantation has long been recognized for its potential in tolerance induction for subsequently transplanted organs. We have recently published that co-administration of Myeloid Progenitor (MP) and third party Hematopoietic Stem Cells (HSC) can induce MP-specific tolerance for subsequently transplanted organs [1].
Mice received an allogeneic HSC and third party MP transplantation simultaneous with placement of a MP-matched skin graft. Variants tested include time of graft placement, MP genotype and source of cells.
Using B10;B6-Rag2(-/-)Il2rg(-/-) mice, we demonstrate that specific tolerance can be induced by MP given simultaneous with the skin graft in the complete absence of MP-donor-matched lymphoid cells. Ex vivo expanded MP function as well as sorted cells in inducing tolerance. In addition we demonstrate that tolerance can be induced by MP in the context of autologous HSC transplantation.
Our results demonstrate that the previously observed expansion of organ donor matched Treg is not essential for tolerance, and that MP tolerance protocols can be envisioned in most clinical settings, including those involving deceased donor organs.
供体特异性造血细胞移植长期以来因其在诱导对随后移植器官的耐受性方面的潜力而受到认可。我们最近发表了髓系祖细胞(MP)与第三方造血干细胞(HSC)联合给药可诱导对随后移植器官的MP特异性耐受性[1]。
小鼠在接受异体HSC和第三方MP移植的同时植入与MP匹配的皮肤移植物。测试的变量包括移植物植入时间、MP基因型和细胞来源。
使用B10;B6-Rag2(-/-)Il2rg(-/-)小鼠,我们证明在完全没有与MP供体匹配的淋巴细胞的情况下,与皮肤移植物同时给予MP可诱导特异性耐受性。体外扩增的MP以及分选细胞在诱导耐受性方面发挥作用。此外,我们证明在自体HSC移植的情况下MP可诱导耐受性。
我们的结果表明,先前观察到的器官供体匹配的调节性T细胞的扩增对于耐受性并非必不可少,并且可以在大多数临床环境中设想MP耐受性方案,包括那些涉及已故供体器官的情况。