Transplantation of retrovirally transduced bone marrow prevents autoimmune disease in aged mice by peripheral tolerance mechanisms

Transplantation of retrovirally transduced bone marrow prevents autoimmune disease in aged mice by peripheral tolerance mechanisms
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DOI:
10.3109/08916934.2010.541173
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发表时间:
2011-08-01
期刊:
影响因子:
3.5
通讯作者:
Chan, James
Chan, James
中科院分区:
医学4区
文献类型:
--
作者:
Chen, Xiang T.;Chan, Siow T.;Chan, James

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研究表明,移植表达自身抗原的骨髓(BM)可保护100%的幼年小鼠免受髓鞘少突胶质细胞糖蛋白(MOG)诱导的实验性自身免疫性脑脊髓炎(EAE)的侵害,其中胸腺克隆缺失是一种耐受机制。在这里,我们询问老年小鼠是否也可以在移植自体抗原工程BM后耐受,以及去势诱导的胸腺再生是否可以增强这一结果。然后,无论去势诱导的胸腺再生如何,50%的老年小鼠都受到了EAE的保护。无EAE和患病小鼠表现出MOG特异性淋巴细胞增殖和抗体产生,而不管去势诱导的胸腺再生,与缺乏胸腺内自身抗原反应性T细胞缺失一致。虽然低嵌合水平(
Transplantation of bone marrow (BM) engineered to express self-antigen has been shown to protect 100% of young mice from myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE), with thymic clonal deletion as a tolerance mechanism. Here, we asked whether aged mice can also be tolerised following transplantation with self-antigen-engineered BM and whether castration-induced thymus regrowth can enhance this outcomes. Then, 50% of aged mice were protected from EAE regardless of castration-induced thymus regrowth. EAE-free and diseased mice demonstrated MOG-specific lymphocyte proliferation and antibody production regardless of castration-induced thymus regrowth, consistent with lack of intrathymic deletion of self-antigen-reactive T cells. Although low chimerism levels (