多发性硬化症中自身反应性T细胞克隆的疫苗接种:免疫学和临床数据概述

Vaccination with autoreactive T cell clones in multiple sclerosis: overview of immunological and clinical data.

作者信息

Stinissen P, Zhang J, Medaer R, Vandevyver C, Raus J

机构信息

Dr. L. Willems-Instituut, Diepenbeek, Belgium.

出版信息

J Neurosci Res. 1996 Aug 15;45(4):500-11. doi: 10.1002/(SICI)1097-4547(19960815)45:4<500::AID-JNR21>3.0.CO;2-2.

Abstract

Although the etiology and pathogenesis of Multiple Sclerosis (MS) remain elusive, accumulating evidence indicates that MS is a chronic inflammatory disease with an autoimmune component, mediated by autoreactive T lymphocytes specific for myelin antigens. The triggering T cell autoantigen has not been identified yet, but recent immunological studies in MS and parallel experiments in experimental allergic encephalomyelitis (EAE), the animal model of MS, have indicated that myelin basic protein (MBP) can be considered as one of the major candidate autoantigens in the pathogenesis of the disease. Based on these observations, several therapeutic strategies have been developed aimed at the specific elimination or inactivation of MBP reactive T cells in MS. One of these approaches involves the immunization of MS patients with autologous attenuated autoreactive T cells to induce an immune response specifically targeted at these autoreactive T cells. This method, termed T cell vaccination, has been shown to prevent and treat EAE. We have recently conducted a pilot trial of T cell vaccination in a limited group of MS patients to evaluate the immunological responses to the injected cells. The data obtained indicate that this type of vaccination induces an effective anti-clonotypic T cell response leading to a specific depletion of circulating MBP reactive T cells. Preliminary data on the clinical effects are promising, encouraging further clinical trials.

摘要

尽管多发性硬化症(MS)的病因和发病机制仍不明确,但越来越多的证据表明,MS是一种具有自身免疫成分的慢性炎症性疾病,由针对髓鞘抗原的自身反应性T淋巴细胞介导。引发T细胞自身抗原尚未确定,但最近对MS的免疫学研究以及在MS动物模型实验性变应性脑脊髓炎(EAE)中的平行实验表明,髓鞘碱性蛋白(MBP)可被视为该疾病发病机制中的主要候选自身抗原之一。基于这些观察结果,已经开发了几种治疗策略,旨在特异性消除或灭活MS中MBP反应性T细胞。其中一种方法是用自体减毒自身反应性T细胞对MS患者进行免疫接种,以诱导针对这些自身反应性T细胞的特异性免疫反应。这种方法被称为T细胞疫苗接种,已被证明可以预防和治疗EAE。我们最近在一小群MS患者中进行了T细胞疫苗接种的试点试验,以评估对注射细胞的免疫反应。获得的数据表明,这种类型的疫苗接种可诱导有效的抗克隆型T细胞反应,导致循环中MBP反应性T细胞的特异性消耗。关于临床效果的初步数据很有希望,这鼓励了进一步的临床试验。

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