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Lpr T细胞对MRL/lpr小鼠的狼疮具有疫苗接种作用。

lpr T cells vaccinate against lupus in MRL/lpr mice.

作者信息

De Alborán I M, Gutierrez J C, Gonzalo J A, Andreu J L, Marcos M A, Kroemer G, Martínez C

机构信息

Centro de Biología Molecular, CSIC, Universidad Autónoma, Madrid, Spain.

出版信息

Eur J Immunol. 1992 Apr;22(4):1089-93. doi: 10.1002/eji.1830220432.

DOI:10.1002/eji.1830220432
PMID:1532360
Abstract

MRL/MP-lpr/lpr mice are homozygous for the lpr mutation that results in the accumulation of phenotypically abnormal cells (CD3+CD4+CD8-) in all lymphoid issues. Although no major abnormalities in the T cell receptor repertoire expressed by such lpr cells have been reported, the lpr mutation is a major disease-accelerating factor. Finally, intravenous administration of irradiated lpr cells recovered from the hyperplastic lymph nodes of adult diseased animals to young MRL/Mp-lpr/lpr mice resulted in a highly significant amelioration of disease parameters. This "T cell vaccination" approach resulted in a selective depletion of cells expressing products of the V beta 8.2 subfamily among lymph node T cells, in addition to eliciting a surge in peripheral T cells capable of conferring disease protection in adoptive transfer experiments. Thus, a strategy aimed at specifically reducing the frequency of lpr cells proved successful in mitigating the autoimmune process. These findings add to the involvement of lpr cells in the autoimmune process and constitute the first report that T cell vaccination may be beneficial to a spontaneously occurring autoimmune disease.

摘要

MRL/MP-lpr/lpr小鼠为lpr突变的纯合子,该突变导致在所有淋巴组织中出现表型异常细胞(CD3+CD4+CD8-)的积累。尽管尚未有关于此类lpr细胞所表达的T细胞受体库存在重大异常的报道,但lpr突变是一个主要的疾病加速因素。最后,将从成年患病动物增生性淋巴结中回收的经辐照的lpr细胞静脉注射给年轻的MRL/Mp-lpr/lpr小鼠,结果导致疾病参数得到高度显著的改善。这种“T细胞疫苗接种”方法除了引发外周T细胞激增,使其在过继转移实验中能够提供疾病保护外,还导致淋巴结T细胞中表达Vβ8.2亚家族产物的细胞选择性耗竭。因此,一种旨在特异性降低lpr细胞频率的策略被证明在减轻自身免疫过程方面是成功的。这些发现进一步证明了lpr细胞参与自身免疫过程,并且是关于T细胞疫苗接种可能对一种自发发生的自身免疫性疾病有益的首次报道。

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1
lpr T cells vaccinate against lupus in MRL/lpr mice.Lpr T细胞对MRL/lpr小鼠的狼疮具有疫苗接种作用。
Eur J Immunol. 1992 Apr;22(4):1089-93. doi: 10.1002/eji.1830220432.
2
Attenuation of autoimmune disease and lymphocyte accumulation in MRL/lpr mice by treatment with anti-V beta 8 antibodies.用抗Vβ8抗体治疗对MRL/lpr小鼠自身免疫性疾病及淋巴细胞聚集的抑制作用
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Intestinal intraepithelial lymphocyte T cells are resistant to lpr gene-induced T cell abnormalities.肠道上皮内淋巴细胞T细胞对lpr基因诱导的T细胞异常具有抗性。
Eur J Immunol. 1992 Jan;22(1):137-45. doi: 10.1002/eji.1830220121.
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beta2-microglobulin dependence of the lupus-like autoimmune syndrome of MRL-lpr mice.MRL-lpr小鼠狼疮样自身免疫综合征对β2-微球蛋白的依赖性
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Lack of association of V beta 8+ T cells with lupus-like syndrome in MRL-lpr/lpr mice.MRL-lpr/lpr小鼠中Vβ8 + T细胞与狼疮样综合征缺乏关联。
Eur J Immunol. 1994 Jul;24(7):1717-20. doi: 10.1002/eji.1830240741.
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The role of the interleukin-2 (IL-2)/IL-2 receptor pathway in MRL/lpr lymphadenopathy: the expanded CD4-8- T cell subset completely lacks functional IL-2 receptors.白细胞介素-2(IL-2)/IL-2受体通路在MRL/lpr淋巴结病中的作用:扩增的CD4 - 8 - T细胞亚群完全缺乏功能性IL-2受体。
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Origin of CD4-CD8-B220+ T cells in MRL-lpr/lpr mice. Clues from a T cell receptor beta transgenic mouse.MRL-lpr/lpr小鼠中CD4-CD8-B220+ T细胞的起源。来自T细胞受体β转基因小鼠的线索。
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Expansion of the population of double negative CD4-8- T alpha beta-cells in the liver is a common feature of autoimmune mice.肝脏中双阴性CD4-8-Tαβ细胞群体的扩增是自身免疫性小鼠的一个常见特征。
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Studies of T cell deletion and T cell anergy following in vivo administration of SEB to normal and lupus-prone mice.对正常小鼠和易患狼疮小鼠体内注射SEB后T细胞缺失和T细胞无反应性的研究。
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Altered expression of self-reactive T cell receptor V beta regions in autoimmune mice.自身免疫小鼠中自身反应性T细胞受体Vβ区的表达改变。
J Immunol. 1990 Mar 15;144(6):2159-66.

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Prenatal Administration of Betamethasone Causes Changes in the T Cell Receptor Repertoire Influencing Development of Autoimmunity.产前给予倍他米松会导致T细胞受体库发生变化,影响自身免疫的发展。
Front Immunol. 2017 Nov 13;8:1505. doi: 10.3389/fimmu.2017.01505. eCollection 2017.
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The mechanisms and applications of T cell vaccination for autoimmune diseases: a comprehensive review.
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Pathogenesis of lupus dermatoses in autoimmune mice. XIX. Attempts to induce subepidermal immunoglobulin deposition in MRL/Mp- +/+ mice.自身免疫小鼠中狼疮性皮肤病的发病机制。第十九部分。诱导MRL/Mp- +/+小鼠表皮下免疫球蛋白沉积的尝试。
Arch Dermatol Res. 1993;285(1-2):20-6. doi: 10.1007/BF00370818.
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Reverse engineering: a model for T-cell vaccination.逆向工程:一种T细胞疫苗接种模型。
Bull Math Biol. 1994 Jul;56(4):687-721. doi: 10.1007/BF02460717.
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Attenuation of lpr-graft-versus-host disease (GVHD) in MRL/lpr spleen cell-injected SCID mice by in vivo treatment with anti-V beta 8.1,2 monoclonal antibody.通过用抗Vβ8.1,2单克隆抗体进行体内治疗,减轻注射MRL/lpr脾细胞的SCID小鼠的lpr移植物抗宿主病(GVHD)。
Clin Exp Immunol. 1994 Jun;96(3):500-7. doi: 10.1111/j.1365-2249.1994.tb06057.x.