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基于眼免疫赦免原理的疗法。

Therapies based on principles of ocular immune privilege.

作者信息

Zhang-Hoover Jie, Stein-Streilein Joan

机构信息

Schepens Eye Research Institute, and Pulmonary and Critical Care Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass., USA.

出版信息

Chem Immunol Allergy. 2007;92:317-327. doi: 10.1159/000099281.

Abstract

Anterior chamber (AC)-associated immune deviation (ACAID) is a form of ocularderived peripheral tolerance that helps to maintain the immune privilege of the eye by suppressing both the priming and elicitation of adaptive immune responses. ACAID is known to facilitate the survival of corneal grafts and suppression autoimmune uveitis in the eye. Intravenous inoculation of in vitro generated ACAID tolerance-inducing antigen presenting cells (APCs) treated with transforming growth factor-Beta2 (tolerogenic APCs) generates the kind of T regulatory cells found in in vivo ACAID when antigen is inoculated into the AC of the eye. Here, we review the application of peripheral tolerance induction by ACAID with either AC inoculation or in vitro generated tolerogenic ACAID-APCs in suppressing ongoing Th1- and Th2-mediated immune pathogenesis in naive and presensitized hosts. Transfer of tolerogenic APCs has suppressed antigen-specific immune inflammation in animal models of experimental autoimmune encephalomyelitis, hapten immune pulmonary interstitial fibrosis, and ovalbumin-induced allergic pulmonary inflammation. The possibility of immune therapy by in vitro generated ACAID-like tolerogenic APCs in humans is discussed.

摘要

前房(AC)相关免疫偏离(ACAID)是一种眼源性外周耐受形式,通过抑制适应性免疫反应的启动和激发来维持眼睛的免疫赦免。已知ACAID有助于角膜移植的存活并抑制眼部自身免疫性葡萄膜炎。静脉注射经转化生长因子-β2处理的体外产生的ACAID耐受诱导抗原呈递细胞(耐受性APC),当抗原接种到眼的前房时,会产生体内ACAID中发现的那种调节性T细胞。在此,我们综述了通过ACAID进行外周耐受诱导(通过前房接种或体外产生的耐受性ACAID-APC)在抑制未致敏和预致敏宿主中正在进行的Th1和Th2介导的免疫发病机制中的应用。耐受性APC的转移已在实验性自身免疫性脑脊髓炎、半抗原免疫性肺间质纤维化和卵清蛋白诱导的过敏性肺部炎症的动物模型中抑制了抗原特异性免疫炎症。还讨论了体外产生的类似ACAID的耐受性APC用于人类免疫治疗的可能性。

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