Myelin reactive T cells after T cell vaccination in multiple sclerosis: cytokine profile and depletion by additional immunizations
Myelin reactive T cells after T cell vaccination in multiple sclerosis: cytokine profile and depletion by additional immunizations
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DOI：
10.1016/s0165-5728(99)00157-5
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发表时间：
2000-01-03
影响因子：
3.3
通讯作者：
Stinissen, P
中科院分区：
文献类型：
--
作者：
Hermans, G;Medaer, R;Stinissen, P
致病性自身反应性T细胞可以通过T细胞疫苗（TCV）来靶向，在这一过程中，患者使用自身减毒的致病性T细胞进行免疫。我们之前报道过，多发性硬化症（MS）患者中带有髓鞘碱性蛋白（MBP）反应性T细胞克隆的TCV诱导T细胞免疫反应，导致所有患者中MBP反应性T细胞克隆耗尽。TCV治疗5年后，9例MS患者中有5例出现MBP反应性T细胞。这些克隆与接种前分离的克隆来源不同。我们研究了这些再生克隆的细胞因子谱、细胞毒性和表位特异性。我们的数据表明，这些克隆表达了与TCV之前分离的克隆相似的效应功能，这表明它们也可能在该疾病中起致病性作用。我们证明了这些克隆可以通过额外的免疫序列来消耗。这些发现可能与MS和其他自身免疫性疾病的其他T细胞靶向免疫疗法有关。(C) 2000 Elsevier Science B.V.版权所有
Pathogenic autoreactive T cells can be targeted by T cell vaccination (TCV), a procedure in which patients are immunized with autologous attenuated pathogenic T cells. We reported previously that TCV with myelin basic protein (MBP) reactive T cell clones in multiple sclerosis (MS) patients induced T cell immune responses, resulting in a clonal depletion of MBP reactive T cells in all patients. Five years after TCV, MBP reactive T cells were observed in five out of nine MS patients. These clones had a different clonal origin from those isolated before vaccination. We have studied the cytokine profile, cytotoxicity and epitope specificity of these reappearing clones. Our data indicate that the clones express similar effector functions as those isolated before TCV, suggesting that they also could play a pathogenic role in the disease. We demonstrated that these clones can be depleted by an additional sequence of immunizations. These findings may be relevant to other T cell targeted immunotherapies for MS and other autoimmune diseases. (C) 2000 Elsevier Science B.V. All rights reserved.