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在易患自身免疫性疾病的MRL/lpr(H-2k)小鼠中,针对意外的H-2d单倍型的自发自身细胞毒性。

Spontaneous autocytotoxicity against an unexpected H-2d haplotype in MRL/lpr (H-2k) autoimmune disease-prone mice.

作者信息

Bobé P, Gachelin G, Kiger N

出版信息

Immunogenetics. 1987;25(4):251-7. doi: 10.1007/BF00404695.

DOI:10.1007/BF00404695
PMID:3494673
Abstract

The MRL/lpr (H-2k) inbred strain, a model for the autoimmune disease systemic lupus erythematosus, differs from the healthy inbred strain MRL +/+ (H-2k) by only 0.1% of its genome. Southern blot analysis using class I and class II probes confirmed the H-2k genotype of both strains. Among the Iak-positive peritoneal cells, cells with an unexpected expression of Iad specificities were detected in a radioimmunoassay using several monoclonal antibodies and one conventional antiserum. This was only found in aged (6- to 9-month-old) mice both in the MRL/lpr strain (32% Iad-positive mice) and in the MRL +/+ strain (42% Iad-positive mice). Furthermore, 24% of aged MRL/lpr mice exhibited strong spontaneous cytotoxic T lymphocyte (CTL) activities against P815 (H-2d) target cells, and 57% had a weaker but still detectable level of cytotoxicity. In contrast, such a CTL activity has never been found in the MRL +/+ strain. These results suggest that the anti-H-2d CTL plays a role in the onset of the autoimmune process in MRL/lpr mice.

摘要

MRL/lpr(H-2k)近交系是自身免疫性疾病系统性红斑狼疮的一种模型,它与健康近交系MRL +/+(H-2k)仅在0.1%的基因组上存在差异。使用I类和II类探针的Southern印迹分析证实了两个品系的H-2k基因型。在Iak阳性的腹膜细胞中,使用几种单克隆抗体和一种传统抗血清进行放射免疫测定时,检测到了具有意外Iad特异性表达的细胞。这种情况仅在老年(6至9个月大)小鼠中发现,在MRL/lpr品系(32%的Iad阳性小鼠)和MRL +/+品系(42%的Iad阳性小鼠)中均有出现。此外,24%的老年MRL/lpr小鼠对P815(H-2d)靶细胞表现出强烈的自发细胞毒性T淋巴细胞(CTL)活性,57%的小鼠具有较弱但仍可检测到的细胞毒性水平。相比之下,在MRL +/+品系中从未发现过这种CTL活性。这些结果表明,抗H-2d CTL在MRL/lpr小鼠自身免疫过程的发病中起作用。

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本文引用的文献

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Graft-versus-host reactions: clues to the etiopathology of a spectrum of immunological diseases.移植物抗宿主反应:一系列免疫性疾病病因病理学的线索
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Monoclonal antibodies to mouse MHC antigens. III. Hybridoma antibodies reacting to antigens of the H-2b haplotype reveal genetic control of isotype expression.抗小鼠主要组织相容性复合体(MHC)抗原的单克隆抗体。III. 与H-2b单倍型抗原发生反应的杂交瘤抗体揭示了同种型表达的遗传控制。
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The isolation and functional characterization of autoimmune clones expressing inappropriate Ia.表达不适当Ia的自身免疫克隆的分离与功能特性分析
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Attempts at standardization of lupus-like graft-vs-host disease: inadvertent repopulation by DBA/2 spleen cells of H-2-different nonirradiated F1 mice.狼疮样移植物抗宿主病标准化的尝试:H-2不同的未受照射F1小鼠被DBA/2脾细胞意外重新定植。
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Stimulation of one particular subset of natural killer cells by peptidoglycans extracted from gram-positive bacteria.
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Proc Natl Acad Sci U S A. 1980 Sep;77(9):5409-13. doi: 10.1073/pnas.77.9.5409.