Sachs David H, Sykes Megan, Yamada Kazuhiko
Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School Boston, Massachusetts, USA.
Transpl Immunol. 2009 Jun;21(2):101-5. doi: 10.1016/j.trim.2008.11.005. Epub 2008 Dec 6.
Because the immunologic differences between species are far greater than those within species, it is likely that the amount of immunosuppression that would be required for successful xenografting would be so much greater than that now used for allografting, that the side-effects and complications would be unacceptable. Tolerance approaches to xenotransplantation would overcome this concern. Studies in humanized mouse models have demonstrated that human T cells can be tolerized to porcine xenografts, providing important proofs of principle of the potential feasibility of pig-to-primate xenograft tolerance. The results available from studies of pig-to-primate xenotransplantation to date have demonstrated that while chronic immunosuppressive drugs have not completely avoided either T cell responses or humoral rejection, approaches directed toward tolerance induction have been encouraging with regard to avoiding immunization at both of these levels.
由于物种之间的免疫差异远大于物种内部的差异,成功进行异种移植所需的免疫抑制量可能会比目前用于同种移植的量大得多,以至于副作用和并发症将是不可接受的。异种移植的耐受性方法将克服这一问题。在人源化小鼠模型中的研究表明,人类T细胞可以对猪异种移植物产生耐受性,这为猪到灵长类动物异种移植耐受性的潜在可行性提供了重要的原理证明。迄今为止,猪到灵长类动物异种移植的研究结果表明,虽然慢性免疫抑制药物尚未完全避免T细胞反应或体液排斥,但在这两个层面上,旨在诱导耐受性的方法在避免免疫方面一直令人鼓舞。