Analysis of the T cell repertoire for myelin basic protein in thymus‐grafted and other types of chimera: evidence that major histocompatibility complex molecules on accessory cells rather than T cell specificity mainly regulate susceptibility to autoimmune encephalomyelitis

Analysis of the T cell repertoire for myelin basic protein in thymus‐grafted and other types of chimera: evidence that major histocompatibility complex molecules on accessory cells rather than T cell specificity mainly regulate susceptibility to autoimmune encephalomyelitis
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胸腺移植和其他类型嵌合体中髓磷脂碱性蛋白的 T 细胞库分析:证据表明辅助细胞上的主要组织相容性复合物分子而不是 T 细胞特异性主要调节对自身免疫性脑脊髓炎的易感性

DOI:
10.1002/eji.1830200934
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发表时间:
1990
影响因子:
5.4
通讯作者:
M. Fujiwara
M. Fujiwara
中科院分区:
医学3区
文献类型:
--
作者:
Y. Matsumoto;K. Kawai;M. Fujiwara

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实验性自身免疫性脑脊髓炎(EAE)是一种T细胞介导的自身免疫性疾病,可通过免疫脑特异性抗原(如髓鞘碱性蛋白(MBP))在啮齿动物中诱导。同样众所周知的是,不同品系的大鼠在主动免疫后对EAE的易感性不同。为了阐明对EAE的易感性和抗性的免疫机制,我们首先使用具有来自EAE易感(LEW)或EAE抗性(BM)品系的胸腺的胸腺切除的嵌合体来检查MBP的T细胞库。结果表明,这些嵌合体的T细胞特异性偏向于移植胸腺。非常有趣的是,携带来自抗性品系的胸腺的嵌合体发展了严重的EAE,在MBP的致脑炎68 - 88序列中保留了一个漏洞。这些发现表明,菌株特异性T细胞库本身不参与EAE易感性的调节。此外,与F1 T细胞和骨髓细胞从不同的菌株重建的嵌合体的分析表明,主要组织相容性复合体(MHC)分子上表达的辅助细胞主要决定易感性或抵抗EAE。最后,我们发现,使用各种近交系和同源大鼠携带RT 1 l或RT 1 n,携带RT 1 l的大鼠EAE的易感性受到背景基因的严重影响,而携带RT 1 n的大鼠EAE的抗性主要由辅助细胞上表达的MHC分子调节,而不受背景基因的影响。
Experimental autoimmune encephalomyelitis (EAE) is a T cell‐mediated autoimmune disease inducible in rodents by immunization of brain‐specific antigens such as myelin basic protein (MBP). It is also well known that various strains of rats differ in their susceptibility to EAE upon active immunization. To elucidate the immune mechanisms of susceptibility and resistance to EAE, we first examined the T cell repertoire for MBP using thymectomized chimeras that possessed thymuses from EAE‐susceptible (LEW) or EAE‐resistant (BM) strains. It was revealed that T cell specificity of these chimeras was skewed toward that of the grafted thymus. Very interestingly, the chimeras bearing thymuses from the resistant strain developed severe EAE, keeping a hole in the encephalitogenic 68‐88 sequence of MBP. These findings suggest that the strain‐specific T cell repertoire itself is not involved in the regulation of EAE susceptibility. Furthermore, the analysis of the chimeras reconstituted with F1 T cells and marrow cells from various strains indicates that the major histocompatibility complex (MHC) molecules expressed on accessory cells primarily determine susceptibility or resistance to EAE. We finally showed, using various inbred and congenic rats carrying RT1l or RT1n, that susceptibility to EAE of rats carrying RT1l is heavily influenced by the background genes, whereas resistance to EAE of rats carrying RT1n is primarily regulated by the MHC molecules expressed on accessory cells without influence of the background genes.
DOI: --
发表时间: 1988
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
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期刊: Journal of immunology (Baltimore, Md. : 1950)
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发表时间: 1985
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
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DOI: --
发表时间: 1989
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
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