West Lori J
Departments of Pediatrics, Surgery and Immunology, Alberta Transplant Institute, University of Alberta, Edmonton, Alberta, Canada.
Curr Opin Organ Transplant. 2016 Feb;21(1):66-73. doi: 10.1097/MOT.0000000000000267.
The phenomenon of tolerance induced during immunologic immaturity has been explored for more than 60 years. Although direct application of neonatal tolerance to organ transplantation in human newborns is limited, exploiting discrete components of neonatal immaturity is proving fruitful.
Two reviews comprehensively considered features and impact of neonatal tolerance as described in the 1950s. Recent imaging studies in mice demonstrated complex functional interactions especially of donor regulatory T cells with emerging neonatal immune components. The propensity of the developing immune system toward tolerance rather than immunity to non-self carbohydrates in ABO-incompatible transplantation was shown using glyconanotechnology tools to have exquisite specificity, and is associated with age-related changes in the B-cell compartment and complement components. Discarded infant thymus was found to be a source of abundant therapeutic regulatory T cells. Erythroid precursors transiently present in newborn mice and humans were shown to have immunosuppressive properties that may contribute to a tolerogenic environment.
Neonatal tolerance has profound impact on immunology well beyond transplantation. Continued exploration of mechanisms underlying the malleability of the developing immune system and exploitation of particular components are leading to tools for immune manipulation beyond infancy.
免疫未成熟期间诱导的耐受现象已被研究了60多年。尽管新生儿耐受在人类新生儿器官移植中的直接应用有限，但利用新生儿未成熟的离散成分已被证明是富有成效的。
两篇综述全面回顾了20世纪50年代所描述的新生儿耐受的特征和影响。最近在小鼠身上的成像研究表明，特别是供体调节性T细胞与新生的新生儿免疫成分之间存在复杂的功能相互作用。利用糖纳米技术工具显示，在ABO不相容移植中，发育中的免疫系统对非自身碳水化合物倾向于耐受而非免疫，具有高度特异性，并且与B细胞区室和补体成分的年龄相关变化有关。发现废弃的婴儿胸腺是丰富的治疗性调节性T细胞的来源。在新生小鼠和人类中短暂存在的红系前体细胞被证明具有免疫抑制特性，这可能有助于形成耐受环境。
新生儿耐受对免疫学的影响远远超出移植领域。对发育中免疫系统可塑性的潜在机制的持续探索以及对特定成分的利用正在催生超越婴儿期的免疫操纵工具。
