Columbia Center for Translational Immunology, Columbia University College of Physicians and Surgeons, New York 10032, USA.
Curr Opin Organ Transplant. 2012 Apr;17(2):162-7. doi: 10.1097/MOT.0b013e328350910c.
This review assesses the recent progress in xenograft rejection by innate immune responses, with a focus on innate cellular xenoreactivity.
Current literature was reviewed for new insights into the role of innate cellular immunity in xenograft rejection. Increasing evidence confirms that vigorous innate immune cell activation is accounted for by a combination of xenoantigen recognition by activating receptors, and incompatibility in inhibitory receptor-ligand interactions. Although both innate humoral and cellular xenoimmune responses are predominantly elicited by preformed and induced xenoreactive antibodies in nonhuman primates following porcine xenotransplantation, innate immune cells can also be activated by xenografts in the absence of antibodies. The latter antibody-independent response will likely persist in recipients even when adaptive xenoimmune responses are suppressed. In addition to xenograft rejection by recipient innate immune cells, phagocytic cells within liver xenografts are also deleterious to recipients by causing thrombocytopenia.
Strategies of overcoming innate immune responses are required for successful clinical xenotransplantation. In addition to developing better immunosuppressive and tolerance induction protocols, endeavors towards further genetic modifications of porcine source animals are ultimately important for successful clinical xenotransplantation.
本文综述了固有免疫反应导致异种移植物排斥反应的最新进展，重点关注固有细胞的异种反应性。
为了深入了解固有细胞免疫在异种移植物排斥反应中的作用，我们对现有文献进行了回顾。越来越多的证据证实，固有免疫细胞的强烈激活是由激活受体识别异种抗原和抑制性受体-配体相互作用的不兼容性共同作用的结果。虽然在非人类灵长类动物接受猪异种移植后，主要是通过预先形成的和诱导的异种反应性抗体引起体液和细胞固有异种免疫反应，但在没有抗体的情况下，固有免疫细胞也可以被异种移植物激活。即使适应性异种免疫反应被抑制，后者的抗体非依赖性反应也可能在受体内持续存在。除了受体内在免疫细胞引起的异种移植物排斥反应外，肝异种移植物内的吞噬细胞也通过引起血小板减少对受者造成损害。
为了成功进行临床异种移植，需要克服固有免疫反应的策略。除了开发更好的免疫抑制和诱导耐受方案外，最终还需要努力对猪源动物进行进一步的基因修饰，以实现成功的临床异种移植。
