High prevalence of autoreactive, neuroantigen-specific CD8+ T cells in multiple sclerosis revealed by novel flow cytometric assay
High prevalence of autoreactive, neuroantigen-specific CD8+ T cells in multiple sclerosis revealed by novel flow cytometric assay
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DOI：
10.1182/blood-2003-11-4025
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发表时间：
2004-06-01
期刊：
影响因子：
20.3
通讯作者：
Karandikar, NJ
中科院分区：
文献类型：
--
作者：
Crawford, MP;Yan, SX;Karandikar, NJ
多发性硬化（MS）是中枢神经系统（CNS）的炎性脱髓鞘疾病，具有提示T细胞介导的病理学特征。大多数先前的报道都集中在CD4（+）T细胞上，其基本假设是MS主要是CD4（+）T辅助细胞1（Th1）介导的疾病。在这份报告中，我们使用了一种新的流式细胞术的方法来评估自身反应性T细胞对各种神经抗原的反应。我们发现针对几种CNS自身抗原的CD4（+）和CD8（+）T细胞在MS患者和健康个体中广泛流行。而CD4（+）反应的分布在不同组中相似，复发缓解型MS患者显示CNS特异性CD8（+）反应的比例较高。与健康受试者相比，MS患者的自身反应性CD4（+）T细胞表现出更分化的Th1表型。同样，MS患者的CNS特异性CD8（+）T细胞应答在功能上与健康个体不同。总的来说，这些研究揭示了MS中I类限制性自身反应性CD8（+）T细胞反应的高患病率，迄今为止尚未得到充分重视。结果强调需要评估MS中的CD4（+）和CD8（+）T细胞应答，并在开发新的治疗策略时考虑这两个亚群。(C)2004年，美国血液学会。
Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system (CNS) with features suggestive of T-cell-mediated pathology. Most prior reports have focused on CD4(+) T cells with the underlying assumption that MS is predominantly a CD4(+) T helper 1 (Th1)-mediated disease. In this report, we used a novel flow cytometric approach to evaluate autoreactive T-cell responses against a large variety of neuroantigenic targets. We found that both CD4(+) and CD8(+) T cells targeted against several CNS autoantigens were widely prevalent in patients with MS and healthy individuals. Whereas the distribution of CD4(+) responses was similar in different groups, patients with relapsing-remitting MS showed a higher proportion of CNS-specific CD8(+) responses. Autoreactive CD4(+) T cells from patients with MS exhibited a more differentiated Th1 phenotype compared with healthy subjects. Similarly, CNS-specific CD8(+) T-cell responses from patients with MS were functionally distinct from those in healthy individuals. Collectively, these studies reveal the high prevalence of class I-restricted autoreactive CD8(+) T-cell responses in MS that has been underappreciated thus far. The results emphasize the need to evaluate both CD4(+) and CD8(+) T-cell responses in MS and to make both subsets a consideration in the development of novel therapeutic strategies. (C) 2004 by The American Society of Hematology.