Strategies for inducing immune tolerance are fundamentally similar across a spectrum of immune-mediated disorders, including allergic disease, autoimmunity, and rejection of allografts. In each case, the objective of establishing an immunoregulatory balance is challenged by variable upswings in effector cell populations and proinflammatory mediators of immunity, requiring careful, and innovative therapeutic intervention to restore stability. The Immune Tolerance Network, an international consortium sponsored by the National Institutes of Health, seeks to advance both the scientific understanding and the clinical success of immune therapies for these disorders, through an innovative and collaborative effort involving clinical trials and mechanistic studies. Over the last decade, scientists have evaluated cell-based ablation and deviation strategies in trials using lymphocyte-specific targeting, induction of host-donor hematopoietic chimerism, induction of antigen-specific immune regulation, and a variety of antigen desensitization approaches. In this article, we review some of the highlights of this experience and discuss the potential for progress, utilizing new insights into regulatory mechanisms and biomarker signatures of tolerance.

中文翻译：

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追求免疫耐受的挑战。

诱导免疫耐受的策略在一系列免疫介导的疾病中基本相似，包括过敏性疾病、自身免疫和同种异体移植排斥。在每种情况下，建立免疫调节平衡的目标都受到效应细胞群和免疫促炎介质的可变上升的挑战，需要谨慎和创新的治疗干预来恢复稳定性。Immune Tolerance Network 是一个由美国国立卫生研究院赞助的国际联盟，旨在通过涉及临床试验和机制研究的创新和协作努力，促进对这些疾病的免疫疗法的科学理解和临床成功。在过去十年中，科学家们在试验中使用淋巴细胞特异性靶向、宿主-供体造血嵌合体的诱导、抗原特异性免疫调节的诱导以及各种抗原脱敏方法评估了基于细胞的消融和偏差策略。在本文中，我们回顾了这次经历的一些亮点，并讨论了取得进展的潜力，利用对调节机制和耐受性生物标志物特征的新见解。