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在多发性硬化症及对照中,对髓鞘蛋白脂蛋白产生反应的自身反应性T细胞和B细胞。

Autoreactive T and B cells responding to myelin proteolipid protein in multiple sclerosis and controls.

作者信息

Sun J B, Olsson T, Wang W Z, Xiao B G, Kostulas V, Fredrikson S, Ekre H P, Link H

机构信息

Department of Neurology, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden.

出版信息

Eur J Immunol. 1991 Jun;21(6):1461-8. doi: 10.1002/eji.1830210620.

DOI:10.1002/eji.1830210620
PMID:1710567
Abstract

The pathogenesis of multiple sclerosis (MS) could involve an autoimmune response to proteolipid protein (PLP). Immunization of experimental animals with this major myelin protein can lead to experimental allergic encephalomyelitis. To identify a possible role of PLP as target antigen in MS, we evaluated T cell immunity to PLP in blood and cerebrospinal fluid (CSF) from patients with MS and controls by counting cells which in response to PLP in short-term cultures secreted interferon-gamma. The PLP-specific B cell response was analyzed by counting cells secreting anti-PLP antibodies. PLP-reactive T cells were detected in blood of most MS patients (mean value 1 per 20,408 mononuclear cells), and at 41-fold higher numbers in CSF (mean 1 per 500 CSF cells). Anti-PLP IgG antibody-secreting cells were detected in blood from most MS patients (mean 1 per 30,303 cells), but such cells were 49-fold more frequent in CSF (mean 1 per 625 cells). PLP-reactive T and B cells were also detected in blood and CSF from control patients, but at much lower numbers. A strong and persistent autoimmune response to PLP as well as to other myelin proteins, enriched in CSF, is proposed to be pathogenetically important in MS.

摘要

多发性硬化症(MS)的发病机制可能涉及针对蛋白脂蛋白(PLP)的自身免疫反应。用这种主要的髓鞘蛋白对实验动物进行免疫可导致实验性变应性脑脊髓炎。为了确定PLP作为MS靶抗原的可能作用,我们通过对短期培养中对PLP有反应并分泌γ干扰素的细胞进行计数,评估了MS患者和对照组血液及脑脊液(CSF)中针对PLP的T细胞免疫。通过对分泌抗PLP抗体的细胞进行计数来分析PLP特异性B细胞反应。在大多数MS患者的血液中检测到了PLP反应性T细胞(平均每20408个单核细胞中有1个),而在脑脊液中的数量则高出41倍(平均每500个脑脊液细胞中有1个)。在大多数MS患者的血液中检测到了分泌抗PLP IgG抗体的细胞(平均每30303个细胞中有1个),但此类细胞在脑脊液中的频率高出49倍(平均每625个细胞中有1个)。在对照患者的血液和脑脊液中也检测到了PLP反应性T细胞和B细胞,但数量要少得多。有人提出,对PLP以及其他富含脑脊液的髓鞘蛋白产生强烈而持续的自身免疫反应在MS的发病机制中具有重要意义。

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Autoreactive T and B cells responding to myelin proteolipid protein in multiple sclerosis and controls.在多发性硬化症及对照中,对髓鞘蛋白脂蛋白产生反应的自身反应性T细胞和B细胞。
Eur J Immunol. 1991 Jun;21(6):1461-8. doi: 10.1002/eji.1830210620.
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T and B cell responses to myelin-oligodendrocyte glycoprotein in multiple sclerosis.多发性硬化症中T细胞和B细胞对髓鞘少突胶质细胞糖蛋白的反应
J Immunol. 1991 Mar 1;146(5):1490-5.
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Autoreactive T lymphocytes in multiple sclerosis determined by antigen-induced secretion of interferon-gamma.通过抗原诱导的γ干扰素分泌确定的多发性硬化症中的自身反应性T淋巴细胞
J Clin Invest. 1990 Sep;86(3):981-5. doi: 10.1172/JCI114800.
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Autoreactive T and B cells in nervous system diseases.神经系统疾病中的自身反应性T细胞和B细胞。
Acta Neurol Scand Suppl. 1993;142:1-56.
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Myelin basic protein and proteolipid protein reactivity of brain- and cerebrospinal fluid-derived T cell clones in multiple sclerosis and postinfectious encephalomyelitis.多发性硬化症和感染后脑脊髓炎中脑源性和脑脊液源性T细胞克隆的髓鞘碱性蛋白和蛋白脂蛋白反应性
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Cells producing antibodies specific for myelin basic protein region 70-89 are predominant in cerebrospinal fluid from patients with multiple sclerosis.产生针对髓鞘碱性蛋白70 - 89区域特异性抗体的细胞在多发性硬化症患者的脑脊液中占主导地位。
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Anti-myelin basic protein and anti-proteolipid protein specific forms of multiple sclerosis.多发性硬化症的抗髓鞘碱性蛋白和抗蛋白脂蛋白特异性形式。
Ann Neurol. 1994 Mar;35(3):280-9. doi: 10.1002/ana.410350307.
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Organ-specific autoantigens induce transforming growth factor-beta mRNA expression in mononuclear cells in multiple sclerosis and myasthenia gravis.器官特异性自身抗原在多发性硬化症和重症肌无力患者的单核细胞中诱导转化生长因子-β mRNA表达。
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[T cell immunity to proteolipid protein (PLP) in multiple sclerosis (MS): identification of DR2-associated PLP determinants and conserved TCR CDR3 motifs].[多发性硬化症(MS)中针对蛋白脂质蛋白(PLP)的T细胞免疫:与DR2相关的PLP决定簇和保守的TCR CDR3基序的鉴定]
Nihon Rinsho. 1994 Nov;52(11):2940-5.
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T-cell recognition of an immunodominant myelin basic protein epitope in multiple sclerosis.多发性硬化症中免疫显性髓鞘碱性蛋白表位的T细胞识别
Nature. 1990 Jul 12;346(6280):183-7. doi: 10.1038/346183a0.

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