Novel technologies to engineer graft for tolerance induction.

Conquering allograft rejection remains an elusive goal in spite of recent breakthroughs in the field of immunosuppression. Much of the problem lies in the toxicity and side effects of long-term use of systemic immunosuppressant drugs, which are sometimes ineffective in controlling rejection, but also hinder establishment of transplant tolerance. In this review, we discuss novel technologies that use grafts engineered with immunomodulatory molecules as a means of inducing tolerance. Several recent studies have demonstrated the feasibility of engineering cells, tissues, or solid organ grafts with immunoregulatory biologics to achieve long termgraft survival without the use of chronic immunosuppression. This approach was shown to primarily change the ratio of T effector versus CD4+CD25+FoxP3+ T regulatory cells within the graft microenvironment in favor of attaining localized tolerance induction and maintenance. Localized immunomodulation using biologic-engineered allografts represent a new paradigm for achieving long term graft survival in the absence of chronic use of immunosuppression. The manipulation of the graft, rather than the recipient, not only ensures short and long-term safety by minimizing the adverse effects of immunosuppression, but also allows retention of immune competency critical for the ability of the recipient to fight infections and cancer.

尽管免疫抑制领域近期取得了一些突破，但克服同种异体移植排斥反应仍然是一个难以实现的目标。问题主要在于长期使用全身性免疫抑制药物的毒性和副作用，这些药物有时无法有效控制排斥反应，还会阻碍移植耐受的建立。在这篇综述中，我们讨论了利用带有免疫调节分子的移植物作为诱导耐受手段的新技术。 近期的几项研究已经证明了利用免疫调节生物制剂对细胞、组织或实体器官移植物进行工程改造以在不使用慢性免疫抑制的情况下实现移植物长期存活的可行性。这种方法主要是改变移植物微环境中T效应细胞与CD4 + CD25 + FoxP3 +调节性T细胞的比例，有利于实现局部耐受的诱导和维持。 使用生物工程同种异体移植物进行局部免疫调节代表了一种在不长期使用免疫抑制的情况下实现移植物长期存活的新模式。对移植物而非受者进行操作，不仅通过最大限度地减少免疫抑制的不良影响确保了短期和长期的安全性，还保留了对受者抵抗感染和癌症能力至关重要的免疫能力。